IKAROS: from chromatin organization to transcriptional elongation control.
Journal
Cell death and differentiation
ISSN: 1476-5403
Titre abrégé: Cell Death Differ
Pays: England
ID NLM: 9437445
Informations de publication
Date de publication:
24 Aug 2023
24 Aug 2023
Historique:
received:
16
03
2023
accepted:
14
08
2023
revised:
26
07
2023
medline:
25
8
2023
pubmed:
25
8
2023
entrez:
24
8
2023
Statut:
aheadofprint
Résumé
IKAROS is a master regulator of cell fate determination in lymphoid and other hematopoietic cells. This transcription factor orchestrates the association of epigenetic regulators with chromatin, ensuring the expression pattern of target genes in a developmental and lineage-specific manner. Disruption of IKAROS function has been associated with the development of acute lymphocytic leukemia, lymphoma, chronic myeloid leukemia and immune disorders. Paradoxically, while IKAROS has been shown to be a tumor suppressor, it has also been identified as a key therapeutic target in the treatment of various forms of hematological malignancies, including multiple myeloma. Indeed, targeted proteolysis of IKAROS is associated with decreased proliferation and increased death of malignant cells. Although the molecular mechanisms have not been elucidated, the expression levels of IKAROS are variable during hematopoiesis and could therefore be a key determinant in explaining how its absence can have seemingly opposite effects. Mechanistically, IKAROS collaborates with a variety of proteins and complexes controlling chromatin organization at gene regulatory regions, including the Nucleosome Remodeling and Deacetylase complex, and may facilitate transcriptional repression or activation of specific genes. Several transcriptional regulatory functions of IKAROS have been proposed. An emerging mechanism of action involves the ability of IKAROS to promote gene repression or activation through its interaction with the RNA polymerase II machinery, which influences pausing and productive transcription at specific genes. This control appears to be influenced by IKAROS expression levels and isoform production. In here, we summarize the current state of knowledge about the biological roles and mechanisms by which IKAROS regulates gene expression. We highlight the dynamic regulation of this factor by post-translational modifications. Finally, potential avenues to explain how IKAROS destruction may be favorable in the treatment of certain hematological malignancies are also explored.
Identifiants
pubmed: 37620540
doi: 10.1038/s41418-023-01212-2
pii: 10.1038/s41418-023-01212-2
doi:
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada)
ID : PJT - 180491
Organisme : Gouvernement du Canada | Natural Sciences and Engineering Research Council of Canada (Conseil de Recherches en Sciences Naturelles et en Génie du Canada)
ID : RGPIN-2021-04110
Informations de copyright
© 2023. The Author(s), under exclusive licence to ADMC Associazione Differenziamento e Morte Cellulare.
Références
Georgopoulos K, Moore DD, Derfler B. Ikaros, an early lymphoid-specific transcription factor and a putative mediator for T cell commitment. Science. 1992;258:808–12.
pubmed: 1439790
doi: 10.1126/science.1439790
Hahm K, Cobb BS, McCarty AS, Brown KE, Klug CA, Lee R, et al. Helios, a T cell-restricted Ikaros family member that quantitatively associates with Ikaros at centromeric heterochromatin. Genes Dev. 1998;12:782–96.
pubmed: 9512513
pmcid: 316626
doi: 10.1101/gad.12.6.782
Kelley CM, Ikeda T, Koipally J, Avitahl N, Wu L, Georgopoulos K, et al. Helios, a novel dimerization partner of Ikaros expressed in the earliest hematopoietic progenitors. Curr Biol. 1998;8:508–15.
pubmed: 9560339
doi: 10.1016/S0960-9822(98)70202-7
Morgan B, Sun L, Avitahl N, Andrikopoulos K, Ikeda T, Gonzales E, et al. Aiolos, a lymphoid restricted transcription factor that interacts with Ikaros to regulate lymphocyte differentiation. Embo J. 1997;16:2004–13.
pubmed: 9155026
pmcid: 1169803
doi: 10.1093/emboj/16.8.2004
Perdomo J, Holmes M, Chong B, Crossley M. Eos and pegasus, two members of the Ikaros family of proteins with distinct DNA binding activities. J Biol Chem. 2000;275:38347–54.
pubmed: 10978333
doi: 10.1074/jbc.M005457200
Sjostedt E, Zhong W, Fagerberg L, Karlsson M, Mitsios N, Adori C, et al. An atlas of the protein-coding genes in the human, pig, and mouse brain. Science. 2020;367:eaay5947.
pubmed: 32139519
doi: 10.1126/science.aay5947
Uhlen M, Bjorling E, Agaton C, Szigyarto CA, Amini B, Andersen E, et al. A human protein atlas for normal and cancer tissues based on antibody proteomics. Mol Cell Proteom. 2005;4:1920–32.
doi: 10.1074/mcp.M500279-MCP200
Uhlen M, Fagerberg L, Hallstrom BM, Lindskog C, Oksvold P, Mardinoglu A, et al. Proteomics. Tissue-based map of the human proteome. Science. 2015;347:1260419.
pubmed: 25613900
doi: 10.1126/science.1260419
Uhlen M, Karlsson MJ, Zhong W, Tebani A, Pou C, Mikes J, et al. A genome-wide transcriptomic analysis of protein-coding genes in human blood cells. Science. 2019;366:eaax9198.
pubmed: 31857451
doi: 10.1126/science.aax9198
Sun L, Liu A, Georgopoulos K. Zinc finger-mediated protein interactions modulate Ikaros activity, a molecular control of lymphocyte development. Embo J. 1996;15:5358–69.
pubmed: 8895580
pmcid: 452279
doi: 10.1002/j.1460-2075.1996.tb00920.x
Javed A, Santos-Franca PL, Mattar P, Cui A, Kassem F, Cayouette M. Ikaros family proteins redundantly regulate temporal patterning in the developing mouse retina. Development. 2023;150:dev200436.
pubmed: 36537580
doi: 10.1242/dev.200436
Georgopoulos K. The making of a lymphocyte: the choice among disparate cell fates and the IKAROS enigma. Genes Dev. 2017;31:439–50.
pubmed: 28385788
pmcid: 5393059
doi: 10.1101/gad.297002.117
Matthias P, Rolink AG. Transcriptional networks in developing and mature B cells. Nat Rev Immunol. 2005;5:497–508.
pubmed: 15928681
doi: 10.1038/nri1633
Shahin T, Kuehn HS, Shoeb MR, Gawriyski L, Giuliani S, Repiscak P, et al. Germline biallelic mutation affecting the transcription factor Helios causes pleiotropic defects of immunity. Sci Immunol. 2021;6:eabe3981.
pubmed: 34826259
pmcid: 7612971
doi: 10.1126/sciimmunol.abe3981
Schwickert TA, Tagoh H, Gultekin S, Dakic A, Axelsson E, Minnich M, et al. Stage-specific control of early B cell development by the transcription factor Ikaros. Nat Immunol. 2014;15:283–93.
pubmed: 24509509
pmcid: 5790181
doi: 10.1038/ni.2828
Molnar A, Georgopoulos K. The Ikaros gene encodes a family of functionally diverse zinc finger DNA-binding proteins. Mol Cell Biol. 1994;14:8292–303.
pubmed: 7969165
pmcid: 359368
Koipally J, Georgopoulos K. Ikaros-CtIP interactions do not require C-terminal binding protein and participate in a deacetylase-independent mode of repression. J Biol Chem. 2002;277:23143–9.
pubmed: 11959865
doi: 10.1074/jbc.M202079200
Ferreiros-Vidal I, Carroll T, Taylor B, Terry A, Liang Z, Bruno L, et al. Genome-wide identification of Ikaros targets elucidates its contribution to mouse B-cell lineage specification and pre-B-cell differentiation. Blood. 2013;121:1769–82.
pubmed: 23303821
doi: 10.1182/blood-2012-08-450114
Geimer Le Lay AS, Oravecz A, Mastio J, Jung C, Marchal P, Ebel C, et al. The tumor suppressor Ikaros shapes the repertoire of notch target genes in T cells. Sci Signal. 2014;7:ra28.
pubmed: 24643801
doi: 10.1126/scisignal.2004545
Kim HJ, Barnitz RA, Kreslavsky T, Brown FD, Moffett H, Lemieux ME, et al. Stable inhibitory activity of regulatory T cells requires the transcription factor Helios. Science. 2015;350:334–9.
pubmed: 26472910
pmcid: 4627635
doi: 10.1126/science.aad0616
Zhang J, Jackson AF, Naito T, Dose M, Seavitt J, Liu F, et al. Harnessing of the nucleosome-remodeling-deacetylase complex controls lymphocyte development and prevents leukemogenesis. Nat Immunol. 2011;13:86–94.
pubmed: 22080921
pmcid: 3868219
doi: 10.1038/ni.2150
Koipally J, Heller EJ, Seavitt JR, Georgopoulos K. Unconventional potentiation of gene expression by Ikaros. J Biol Chem. 2002;277:13007–15.
pubmed: 11799125
doi: 10.1074/jbc.M111371200
Marke R, van Leeuwen FN, Scheijen B. The many faces of IKZF1 in B-cell precursor acute lymphoblastic leukemia. Haematologica. 2018;103:565–74.
pubmed: 29519871
pmcid: 5865415
doi: 10.3324/haematol.2017.185603
Caballero R, Setien F, Lopez-Serra L, Boix-Chornet M, Fraga MF, Ropero S, et al. Combinatorial effects of splice variants modulate function of Aiolos. J Cell Sci. 2007;120:2619–30.
pubmed: 17646674
doi: 10.1242/jcs.007344
Payne KJ, Huang G, Sahakian E, Zhu JY, Barteneva NS, Barsky LW, et al. Ikaros isoform x is selectively expressed in myeloid differentiation. J Immunol. 2003;170:3091–8.
pubmed: 12626565
doi: 10.4049/jimmunol.170.6.3091
Klug CA, Morrison SJ, Masek M, Hahm K, Smale ST, Weissman IL. Hematopoietic stem cells and lymphoid progenitors express different Ikaros isoforms, and Ikaros is localized to heterochromatin in immature lymphocytes. Proc Natl Acad Sci USA. 1998;95:657–62.
pubmed: 9435248
pmcid: 18476
doi: 10.1073/pnas.95.2.657
Bellavia D, Mecarozzi M, Campese AF, Grazioli P, Gulino A, Screpanti I. Notch and Ikaros: not only converging players in T cell leukemia. Cell Cycle. 2007;6:2730–4.
pubmed: 18032925
doi: 10.4161/cc.6.22.4894
McCarty AS, Kleiger G, Eisenberg D, Smale ST. Selective dimerization of a C2H2 zinc finger subfamily. Mol Cell. 2003;11:459–70.
pubmed: 12620233
doi: 10.1016/S1097-2765(03)00043-1
Georgopoulos K. Haematopoietic cell-fate decisions, chromatin regulation and ikaros. Nat Rev Immunol. 2002;2:162–74.
pubmed: 11913067
doi: 10.1038/nri747
Rebollo A, Schmitt C. Ikaros, Aiolos and Helios: transcription regulators and lymphoid malignancies. Immunol Cell Biol. 2003;81:171–5.
pubmed: 12752680
doi: 10.1046/j.1440-1711.2003.01159.x
Heizmann B, Kastner P, Chan S. The Ikaros family in lymphocyte development. Curr Opin Immunol. 2018;51:14–23.
pubmed: 29278858
doi: 10.1016/j.coi.2017.11.005
Schjerven H, McLaughlin J, Arenzana TL, Frietze S, Cheng D, Wadsworth SE, et al. Selective regulation of lymphopoiesis and leukemogenesis by individual zinc fingers of Ikaros. Nat Immunol. 2013;14:1073–83.
pubmed: 24013668
pmcid: 3800053
doi: 10.1038/ni.2707
Arenzana TL, Schjerven H, Smale ST. Regulation of gene expression dynamics during developmental transitions by the Ikaros transcription factor. Genes Dev. 2015;29:1801–16.
pubmed: 26314708
pmcid: 4573854
doi: 10.1101/gad.266999.115
Lo K, Landau NR, Smale ST. LyF-1, a transcriptional regulator that interacts with a novel class of promoters for lymphocyte-specific genes. Mol Cell Biol. 1991;11:5229–43.
pubmed: 1922043
pmcid: 361569
Thompson EC, Cobb BS, Sabbattini P, Meixlsperger S, Parelho V, Liberg D, et al. Ikaros DNA-binding proteins as integral components of B cell developmental-stage-specific regulatory circuits. Immunity. 2007;26:335–44.
pubmed: 17363301
doi: 10.1016/j.immuni.2007.02.010
Gomez-del Arco P, Kashiwagi M, Jackson AF, Naito T, Zhang J, Liu F, et al. Alternative promoter usage at the Notch1 locus supports ligand-independent signaling in T cell development and leukemogenesis. Immunity. 2010;33:685–98.
pubmed: 21093322
pmcid: 3072037
doi: 10.1016/j.immuni.2010.11.008
Ng SY, Yoshida T, Zhang J, Georgopoulos K. Genome-wide lineage-specific transcriptional networks underscore Ikaros-dependent lymphoid priming in hematopoietic stem cells. Immunity. 2009;30:493–507.
pubmed: 19345118
pmcid: 3012962
doi: 10.1016/j.immuni.2009.01.014
Oravecz A, Apostolov A, Polak K, Jost B, Le Gras S, Chan S, et al. Ikaros mediates gene silencing in T cells through Polycomb repressive complex 2. Nat Commun. 2015;6:8823.
pubmed: 26549758
doi: 10.1038/ncomms9823
Kashiwagi M, Figueroa DS, Ay F, Morgan BA, Georgopoulos K. A double-negative thymocyte-specific enhancer augments Notch1 signaling to direct early T cell progenitor expansion, lineage restriction and beta-selection. Nat Immunol. 2022;23:1628–43.
pubmed: 36316479
pmcid: 10187983
doi: 10.1038/s41590-022-01322-y
Mullighan C, Downing J. Ikaros and acute leukemia. Leuk Lymphoma. 2008;49:847–9.
pubmed: 18464105
doi: 10.1080/10428190801947500
Boutboul D, Kuehn HS, Van de Wyngaert Z, Niemela JE, Callebaut I, Stoddard J, et al. Dominant-negative IKZF1 mutations cause a T, B, and myeloid cell combined immunodeficiency. J Clin Invest. 2018;128:3071–87.
pubmed: 29889099
pmcid: 6026000
doi: 10.1172/JCI98164
Churchman ML, Qian M, Te Kronnie G, Zhang R, Yang W, Zhang H, et al. Germline genetic IKZF1 variation and predisposition to childhood acute lymphoblastic leukemia. Cancer Cell. 2018;33:937–48 e8.
pubmed: 29681510
pmcid: 5953820
doi: 10.1016/j.ccell.2018.03.021
Kuehn HS, Niemela JE, Stoddard J, Mannurita SC, Shahin T, Goel S, et al. Germline IKAROS dimerization haploinsufficiency causes hematologic cytopenias and malignancies. Blood. 2021;137:349–63.
pubmed: 32845957
pmcid: 7819759
doi: 10.1182/blood.2020007292
Nunes-Santos CJ, Kuehn HS, Rosenzweig SD. IKAROS family zinc finger 1-associated diseases in primary immunodeficiency patients. Immunol Allergy Clin North Am. 2020;40:461–70.
pubmed: 32654692
pmcid: 7394939
doi: 10.1016/j.iac.2020.04.004
Yoshida N, Sakaguchi H, Muramatsu H, Okuno Y, Song C, Dovat S, et al. Germline IKAROS mutation associated with primary immunodeficiency that progressed to T-cell acute lymphoblastic leukemia. Leukemia. 2017;31:1221–3.
pubmed: 28096536
doi: 10.1038/leu.2017.25
Lyon de Ana C, Arakcheeva K, Agnihotri P, Derosia N, Winandy S. Lack of ikaros deregulates inflammatory gene programs in T cells. J Immunol. 2019;202:1112–23.
pubmed: 30635395
doi: 10.4049/jimmunol.1801270
Rivellese F, Manou-Stathopoulou S, Mauro D, Goldmann K, Pyne D, Rajakariar R, et al. Effects of targeting the transcription factors Ikaros and Aiolos on B cell activation and differentiation in systemic lupus erythematosus. Lupus Sci Med. 2021;8:e000445.
pubmed: 33727237
pmcid: 7970264
doi: 10.1136/lupus-2020-000445
Kuehn HS, Boast B, Rosenzweig SD. Inborn errors of human IKAROS: LOF and GOF variants associated with primary immunodeficiency. Clin Exp Immunol. 2023;212:129–36.
pubmed: 36433803
doi: 10.1093/cei/uxac109
Sun L, Goodman PA, Wood CM, Crotty ML, Sensel M, Sather H, et al. Expression of aberrantly spliced oncogenic ikaros isoforms in childhood acute lymphoblastic leukemia. J Clin Oncol. 1999;17:3753–66.
pubmed: 10577847
doi: 10.1200/JCO.1999.17.12.3753
Sun L, Heerema N, Crotty L, Wu X, Navara C, Vassilev A, et al. Expression of dominant-negative and mutant isoforms of the antileukemic transcription factor Ikaros in infant acute lymphoblastic leukemia. Proc Natl Acad Sci USA. 1999;96:680–5.
pubmed: 9892693
pmcid: 15196
doi: 10.1073/pnas.96.2.680
Beer PA, Knapp DJ, Kannan N, Miller PH, Babovic S, Bulaeva E, et al. A dominant-negative isoform of IKAROS expands primitive normal human hematopoietic cells. Stem Cell Rep. 2014;3:841–57.
doi: 10.1016/j.stemcr.2014.09.006
Mullighan CG, Miller CB, Radtke I, Phillips LA, Dalton J, Ma J, et al. BCR-ABL1 lymphoblastic leukaemia is characterized by the deletion of Ikaros. Nature. 2008;453:110–4.
pubmed: 18408710
doi: 10.1038/nature06866
Cobb BS, Morales-Alcelay S, Kleiger G, Brown KE, Fisher AG, Smale ST. Targeting of Ikaros to pericentromeric heterochromatin by direct DNA binding. Genes Dev. 2000;14:2146–60.
pubmed: 10970879
pmcid: 316893
doi: 10.1101/gad.816400
Iacobucci I, Storlazzi CT, Cilloni D, Lonetti A, Ottaviani E, Soverini S, et al. Identification and molecular characterization of recurrent genomic deletions on 7p12 in the IKZF1 gene in a large cohort of BCR-ABL1-positive acute lymphoblastic leukemia patients: on behalf of Gruppo Italiano Malattie Ematologiche dell’Adulto Acute Leukemia Working Party (GIMEMA AL WP). Blood. 2009;114:2159–67.
pubmed: 19589926
doi: 10.1182/blood-2008-08-173963
Tonnelle C, Bardin F, Maroc C, Imbert AM, Campa F, Dalloul A, et al. Forced expression of the Ikaros 6 isoform in human placental blood CD34(+) cells impairs their ability to differentiate toward the B-lymphoid lineage. Blood. 2001;98:2673–80.
pubmed: 11675337
doi: 10.1182/blood.V98.9.2673
Beer PA, Knapp DJ, Miller PH, Kannan N, Sloma I, Heel K, et al. Disruption of IKAROS activity in primitive chronic-phase CML cells mimics myeloid disease progression. Blood. 2015;125:504–15.
pubmed: 25370416
pmcid: 4300391
doi: 10.1182/blood-2014-06-581173
Dupuis A, Gaub MP, Legrain M, Drenou B, Mauvieux L, Lutz P, et al. Biclonal and biallelic deletions occur in 20% of B-ALL cases with IKZF1 mutations. Leukemia. 2013;27:503–7.
pubmed: 22868967
doi: 10.1038/leu.2012.204
Iacobucci I, Iraci N, Messina M, Lonetti A, Chiaretti S, Valli E, et al. IKAROS deletions dictate a unique gene expression signature in patients with adult B-cell acute lymphoblastic leukemia. PLoS One. 2012;7:e40934.
pubmed: 22848414
pmcid: 3405023
doi: 10.1371/journal.pone.0040934
Joshi I, Yoshida T, Jena N, Qi X, Zhang J, Van Etten RA, et al. Loss of Ikaros DNA-binding function confers integrin-dependent survival on pre-B cells and progression to acute lymphoblastic leukemia. Nat Immunol. 2014;15:294–304.
pubmed: 24509510
pmcid: 4494688
doi: 10.1038/ni.2821
Kastner P, Dupuis A, Gaub MP, Herbrecht R, Lutz P, Chan S. Function of Ikaros as a tumor suppressor in B cell acute lymphoblastic leukemia. Am J Blood Res. 2013;3:1–13.
pubmed: 23358883
pmcid: 3555193
Mullighan CG, Goorha S, Radtke I, Miller CB, Coustan-Smith E, Dalton JD, et al. Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia. Nature. 2007;446:758–64.
pubmed: 17344859
doi: 10.1038/nature05690
Koipally J, Georgopoulos K. Ikaros interactions with CtBP reveal a repression mechanism that is independent of histone deacetylase activity. J Biol Chem. 2000;275:19594–602.
pubmed: 10766745
doi: 10.1074/jbc.M000254200
Allman D, Sambandam A, Kim S, Miller JP, Pagan A, Well D, et al. Thymopoiesis independent of common lymphoid progenitors. Nat Immunol. 2003;4:168–74.
pubmed: 12514733
doi: 10.1038/ni878
Yoshida T, Ng SY, Zuniga-Pflucker JC, Georgopoulos K. Early hematopoietic lineage restrictions directed by Ikaros. Nat Immunol. 2006;7:382–91.
pubmed: 16518393
doi: 10.1038/ni1314
Georgopoulos K, Bigby M, Wang JH, Molnar A, Wu P, Winandy S, et al. The Ikaros gene is required for the development of all lymphoid lineages. Cell. 1994;79:143–56.
pubmed: 7923373
doi: 10.1016/0092-8674(94)90407-3
Wang JH, Nichogiannopoulou A, Wu L, Sun L, Sharpe AH, Bigby M, et al. Selective defects in the development of the fetal and adult lymphoid system in mice with an Ikaros null mutation. Immunity. 1996;5:537–49.
pubmed: 8986714
doi: 10.1016/S1074-7613(00)80269-1
Bank A. Regulation of human fetal hemoglobin: new players, new complexities. Blood. 2006;107:435–43.
pubmed: 16109777
pmcid: 1895603
doi: 10.1182/blood-2005-05-2113
Bottardi S, Ross J, Bourgoin V, Fotouhi-Ardakani N, Affar el B, Trudel M, et al. Ikaros and GATA-1 combinatorial effect is required for silencing of human gamma-globin genes. Mol Cell Biol. 2009;29:1526–37.
pubmed: 19114560
doi: 10.1128/MCB.01523-08
Cytlak U, Resteu A, Bogaert D, Kuehn HS, Altmann T, Gennery A, et al. Ikaros family zinc finger 1 regulates dendritic cell development and function in humans. Nat Commun. 2018;9:1239.
pubmed: 29588478
pmcid: 5869589
doi: 10.1038/s41467-018-02977-8
Dumortier A, Kirstetter P, Kastner P, Chan S. Ikaros regulates neutrophil differentiation. Blood. 2003;101:2219–26.
pubmed: 12406904
doi: 10.1182/blood-2002-05-1336
Malinge S, Thiollier C, Chlon TM, Dore LC, Diebold L, Bluteau O, et al. Ikaros inhibits megakaryopoiesis through functional interaction with GATA-1 and NOTCH signaling. Blood. 2013;121:2440–51.
pubmed: 23335373
pmcid: 3612856
doi: 10.1182/blood-2012-08-450627
Oh KS, Gottschalk RA, Lounsbury NW, Sun J, Dorrington MG, Baek S, et al. Dual roles for ikaros in regulation of macrophage chromatin state and inflammatory gene expression. J Immunol. 2018;201:757–71.
pubmed: 29898962
doi: 10.4049/jimmunol.1800158
Toubai T, Sun Y, Tawara I, Friedman A, Liu C, Evers R, et al. Ikaros-Notch axis in host hematopoietic cells regulates experimental graft-versus-host disease. Blood. 2011;118:192–204.
pubmed: 21471527
pmcid: 3139384
doi: 10.1182/blood-2010-12-324616
Powell MD, Read KA, Sreekumar BK, Oestreich KJ. Ikaros zinc finger transcription factors: regulators of cytokine signaling pathways and CD4(+) T helper cell differentiation. Front Immunol. 2019;10:1299.
pubmed: 31244845
pmcid: 6563078
doi: 10.3389/fimmu.2019.01299
Read KA, Jones DM, Freud AG, Oestreich KJ. Established and emergent roles for Ikaros transcription factors in lymphoid cell development and function. Immunol Rev. 2021;300:82–99.
pubmed: 33331000
doi: 10.1111/imr.12936
Cippitelli M, Stabile H, Kosta A, Petillo S, Gismondi A, Santoni A, et al. Role of Aiolos and Ikaros in the antitumor and immunomodulatory activity of IMiDs in multiple myeloma: better to lose than to find them. Int J Mol Sci. 2021;22:1103.
pubmed: 33499314
pmcid: 7865245
doi: 10.3390/ijms22031103
Koipally J, Renold A, Kim J, Georgopoulos K. Repression by Ikaros and Aiolos is mediated through histone deacetylase complexes. Embo J. 1999;18:3090–100.
pubmed: 10357820
pmcid: 1171390
doi: 10.1093/emboj/18.11.3090
Sabbattini P, Lundgren M, Georgiou A, Chow C, Warnes G, Dillon N. Binding of Ikaros to the lambda5 promoter silences transcription through a mechanism that does not require heterochromatin formation. Embo J. 2001;20:2812–22.
pubmed: 11387214
pmcid: 125479
doi: 10.1093/emboj/20.11.2812
Zhou N, Gutierrez-Uzquiza A, Zheng XY, Chang R, Vogl DT, Garfall AL, et al. RUNX proteins desensitize multiple myeloma to lenalidomide via protecting IKZFs from degradation. Leukemia. 2019;33:2006–21.
pubmed: 30760870
pmcid: 6687534
doi: 10.1038/s41375-019-0403-2
Bottardi S, Mavoungou L, Bourgoin V, Mashtalir N, Affar el B, Milot E. Direct protein interactions are responsible for Ikaros-GATA and Ikaros-Cdk9 cooperativeness in hematopoietic cells. Mol Cell Biol. 2013;33:3064–76.
pubmed: 23732910
pmcid: 3753914
doi: 10.1128/MCB.00296-13
Novershtern N, Subramanian A, Lawton LN, Mak RH, Haining WN, McConkey ME, et al. Densely interconnected transcriptional circuits control cell states in human hematopoiesis. Cell. 2011;144:296–309.
pubmed: 21241896
pmcid: 3049864
doi: 10.1016/j.cell.2011.01.004
Ross J, Mavoungou L, Bresnick EH, Milot E. GATA-1 utilizes Ikaros and polycomb repressive complex 2 to suppress Hes1 and to promote erythropoiesis. Mol Cell Biol. 2012;32:3624–38.
pubmed: 22778136
pmcid: 3430200
doi: 10.1128/MCB.00163-12
Bottardi S, Zmiri FA, Bourgoin V, Ross J, Mavoungou L, Milot E. Ikaros interacts with P-TEFb and cooperates with GATA-1 to enhance transcription elongation. Nucleic Acids Res. 2011;39:3505–19.
pubmed: 21245044
pmcid: 3089448
doi: 10.1093/nar/gkq1271
Johnson KD, Grass JA, Boyer ME, Kiekhaefer CM, Blobel GA, Weiss MJ, et al. Cooperative activities of hematopoietic regulators recruit RNA polymerase II to a tissue-specific chromatin domain. Proc Natl Acad Sci USA. 2002;99:11760–5.
pubmed: 12193659
pmcid: 129342
doi: 10.1073/pnas.192285999
Vakoc CR, Letting DL, Gheldof N, Sawado T, Bender MA, Groudine M, et al. Proximity among distant regulatory elements at the beta-globin locus requires GATA-1 and FOG-1. Mol Cell. 2005;17:453–62.
pubmed: 15694345
doi: 10.1016/j.molcel.2004.12.028
Sridharan R, Smale ST. Predominant interaction of both Ikaros and Helios with the NuRD complex in immature thymocytes. J Biol Chem. 2007;282:30227–38.
pubmed: 17681952
doi: 10.1074/jbc.M702541200
Kim J, Sif S, Jones B, Jackson A, Koipally J, Heller E, et al. Ikaros DNA-binding proteins direct formation of chromatin remodeling complexes in lymphocytes. Immunity. 1999;10:345–55.
pubmed: 10204490
doi: 10.1016/S1074-7613(00)80034-5
Dumortier A, Jeannet R, Kirstetter P, Kleinmann E, Sellars M, dos Santos NR, et al. Notch activation is an early and critical event during T-Cell leukemogenesis in Ikaros-deficient mice. Mol Cell Biol. 2006;26:209–20.
pubmed: 16354692
pmcid: 1317628
doi: 10.1128/MCB.26.1.209-220.2006
Bottardi S, Mavoungou L, Milot E. IKAROS: a multifunctional regulator of the polymerase II transcription cycle. Trends Genet. 2015;31:500–8.
pubmed: 26049627
doi: 10.1016/j.tig.2015.05.003
Lemarie M, Bottardi S, Mavoungou L, Pak H, Milot E. IKAROS is required for the measured response of NOTCH target genes upon external NOTCH signaling. PLoS Genet. 2021;17:e1009478.
pubmed: 33770102
pmcid: 8026084
doi: 10.1371/journal.pgen.1009478
Lai AY, Wade PA. Cancer biology and NuRD: a multifaceted chromatin remodelling complex. Nat Rev Cancer. 2011;11:588–96.
pubmed: 21734722
pmcid: 4157524
doi: 10.1038/nrc3091
Nitarska J, Smith JG, Sherlock WT, Hillege MM, Nott A, Barshop WD, et al. A functional switch of NuRD chromatin remodeling complex subunits regulates mouse cortical development. Cell Rep. 2016;17:1683–98.
pubmed: 27806305
pmcid: 5149529
doi: 10.1016/j.celrep.2016.10.022
Loughran SJ, Comoglio F, Hamey FK, Giustacchini A, Errami Y, Earp E, et al. Mbd3/NuRD controls lymphoid cell fate and inhibits tumorigenesis by repressing a B cell transcriptional program. J Exp Med. 2017;214:3085–104.
pubmed: 28899870
pmcid: 5626393
doi: 10.1084/jem.20161827
Iurlaro M, Ficz G, Oxley D, Raiber EA, Bachman M, Booth MJ, et al. A screen for hydroxymethylcytosine and formylcytosine binding proteins suggests functions in transcription and chromatin regulation. Genome Biol. 2013;14:R119.
pubmed: 24156278
pmcid: 4014808
doi: 10.1186/gb-2013-14-10-r119
Yildirim O, Li R, Hung JH, Chen PB, Dong X, Ee LS, et al. Mbd3/NURD complex regulates expression of 5-hydroxymethylcytosine marked genes in embryonic stem cells. Cell. 2011;147:1498–510.
pubmed: 22196727
pmcid: 3252821
doi: 10.1016/j.cell.2011.11.054
Bottardi S, Mavoungou L, Pak H, Daou S, Bourgoin V, Lakehal YA, et al. The IKAROS interaction with a complex including chromatin remodeling and transcription elongation activities is required for hematopoiesis. PLoS Genet. 2014;10:e1004827.
pubmed: 25474253
pmcid: 4256266
doi: 10.1371/journal.pgen.1004827
Zhang W, Aubert A, Gomez de Segura JM, Karuppasamy M, Basu S, Murthy AS, et al. The nucleosome remodeling and deacetylase complex NuRD is built from preformed catalytically active sub-modules. J Mol Biol. 2016;428:2931–42.
pubmed: 27117189
pmcid: 4942838
doi: 10.1016/j.jmb.2016.04.025
Low JK, Webb SR, Silva AP, Saathoff H, Ryan DP, Torrado M, et al. CHD4 is a peripheral component of the nucleosome remodeling and deacetylase complex. J Biol Chem. 2016;291:15853–66.
pubmed: 27235397
pmcid: 4957066
doi: 10.1074/jbc.M115.707018
Zhang T, Wei G, Millard CJ, Fischer R, Konietzny R, Kessler BM, et al. A variant NuRD complex containing PWWP2A/B excludes MBD2/3 to regulate transcription at active genes. Nat Commun. 2018;9:3798.
pubmed: 30228260
pmcid: 6143588
doi: 10.1038/s41467-018-06235-9
Harker N, Garefalaki A, Menzel U, Ktistaki E, Naito T, Georgopoulos K, et al. Pre-TCR signaling and CD8 gene bivalent chromatin resolution during thymocyte development. J Immunol. 2011;186:6368–77.
pubmed: 21515796
doi: 10.4049/jimmunol.1003567
O’Neill DW, Schoetz SS, Lopez RA, Castle M, Rabinowitz L, Shor E, et al. An ikaros-containing chromatin-remodeling complex in adult-type erythroid cells. Mol Cell Biol. 2000;20:7572–82.
pubmed: 11003653
pmcid: 86310
doi: 10.1128/MCB.20.20.7572-7582.2000
Bonifer C, Cockerill PN. Chromatin priming of genes in development: concepts, mechanisms and consequences. Exp Hematol. 2017;49:1–8.
pubmed: 28185904
doi: 10.1016/j.exphem.2017.01.003
Dillon N. Factor mediated gene priming in pluripotent stem cells sets the stage for lineage specification. Bioessays. 2012;34:194–204.
pubmed: 22247014
doi: 10.1002/bies.201100137
Fisher CL, Fisher AG. Chromatin states in pluripotent, differentiated, and reprogrammed cells. Curr Opin Genet Dev. 2011;21:140–6.
pubmed: 21316216
doi: 10.1016/j.gde.2011.01.015
Bernstein BE, Mikkelsen TS, Xie X, Kamal M, Huebert DJ, Cuff J, et al. A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell. 2006;125:315–26.
pubmed: 16630819
doi: 10.1016/j.cell.2006.02.041
Voigt P, Tee WW, Reinberg D. A double take on bivalent promoters. Genes Dev. 2013;27:1318–38.
pubmed: 23788621
pmcid: 3701188
doi: 10.1101/gad.219626.113
Mohd-Sarip A, Teeuwssen M, Bot AG, De Herdt MJ, Willems SM, Baatenburg de Jong RJ, et al. DOC1-dependent recruitment of NURD reveals antagonism with SWI/SNF during epithelial-mesenchymal transition in oral cancer cells. Cell Rep. 2017;20:61–75.
pubmed: 28683324
doi: 10.1016/j.celrep.2017.06.020
Bornelov S, Reynolds N, Xenophontos M, Gharbi S, Johnstone E, Floyd R, et al. The nucleosome remodeling and deacetylation complex modulates chromatin structure at sites of active transcription to fine-tune gene expression. Mol Cell. 2018;71:56–72.e4.
pubmed: 30008319
pmcid: 6039721
doi: 10.1016/j.molcel.2018.06.003
Ho L, Miller EL, Ronan JL, Ho WQ, Jothi R, Crabtree GR. esBAF facilitates pluripotency by conditioning the genome for LIF/STAT3 signalling and by regulating polycomb function. Nat Cell Biol. 2011;13:903–13.
pubmed: 21785422
pmcid: 3155811
doi: 10.1038/ncb2285
King HW, Klose RJ. The pioneer factor OCT4 requires the chromatin remodeller BRG1 to support gene regulatory element function in mouse embryonic stem cells. Elife. 2017;6:e22631.
pubmed: 28287392
pmcid: 5400504
doi: 10.7554/eLife.22631
Li Y, Schulz VP, Deng C, Li G, Shen Y, Tusi BK, et al. Setd1a and NURF mediate chromatin dynamics and gene regulation during erythroid lineage commitment and differentiation. Nucleic Acids Res. 2016;44:7173–88.
pubmed: 27141965
pmcid: 5009724
Bottardi S, Aumont A, Grosveld F, Milot E. Developmental stage-specific epigenetic control of human beta-globin gene expression is potentiated in hematopoietic progenitor cells prior to their transcriptional activation. Blood. 2003;102:3989–97.
pubmed: 12920025
doi: 10.1182/blood-2003-05-1540
Keys JR, Tallack MR, Zhan Y, Papathanasiou P, Goodnow CC, Gaensler KM, et al. A mechanism for Ikaros regulation of human globin gene switching. Br J Haematol. 2008;141:398–406.
pubmed: 18318763
van Lohuizen M. The trithorax-group and polycomb-group chromatin modifiers: implications for disease. Curr Opin Genet Dev. 1999;9:355–61.
pubmed: 10377289
doi: 10.1016/S0959-437X(99)80053-7
Xia L, Huang W, Bellani M, Seidman MM, Wu K, Fan D, et al. CHD4 has oncogenic functions in initiating and maintaining epigenetic suppression of multiple tumor suppressor genes. Cancer Cell. 2017;31:653–68.e7.
pubmed: 28486105
pmcid: 5587180
doi: 10.1016/j.ccell.2017.04.005
Marcon E, Ni Z, Pu S, Turinsky AL, Trimble SS, Olsen JB, et al. Human-chromatin-related protein interactions identify a demethylase complex required for chromosome segregation. Cell Rep. 2014;8:297–310.
pubmed: 24981860
doi: 10.1016/j.celrep.2014.05.050
Hoffmeister H, Fuchs A, Erdel F, Pinz S, Grobner-Ferreira R, Bruckmann A, et al. CHD3 and CHD4 form distinct NuRD complexes with different yet overlapping functionality. Nucleic Acids Res. 2017;45:10534–54.
pubmed: 28977666
pmcid: 5737555
doi: 10.1093/nar/gkx711
Oliviero G, Brien GL, Waston A, Streubel G, Jerman E, Andrews D, et al. Dynamic protein interactions of the polycomb repressive complex 2 during differentiation of pluripotent cells. Mol Cell Proteom. 2016;15:3450–60.
doi: 10.1074/mcp.M116.062240
Wang J, Yu X, Gong W, Liu X, Park KS, Ma A, et al. EZH2 noncanonically binds cMyc and p300 through a cryptic transactivation domain to mediate gene activation and promote oncogenesis. Nat Cell Biol. 2022;24:384–99.
pubmed: 35210568
pmcid: 9710513
doi: 10.1038/s41556-022-00850-x
Reynolds N, Latos P, Hynes-Allen A, Loos R, Leaford D, O’Shaughnessy A, et al. NuRD suppresses pluripotency gene expression to promote transcriptional heterogeneity and lineage commitment. Cell Stem Cell. 2012;10:583–94.
pubmed: 22560079
pmcid: 3402183
doi: 10.1016/j.stem.2012.02.020
Bottardi S, Ross J, Pierre-Charles N, Blank V, Milot E. Lineage-specific activators affect beta-globin locus chromatin in multipotent hematopoietic progenitors. Embo J. 2006;25:3586–95.
pubmed: 16858401
pmcid: 1538551
doi: 10.1038/sj.emboj.7601232
Zhou VW, Goren A, Bernstein BE. Charting histone modifications and the functional organization of mammalian genomes. Nat Rev Genet. 2011;12:7–18.
pubmed: 21116306
doi: 10.1038/nrg2905
Shilatifard A. Molecular implementation and physiological roles for histone H3 lysine 4 (H3K4) methylation. Curr Opin Cell Biol. 2008;20:341–8.
pubmed: 18508253
pmcid: 2504688
doi: 10.1016/j.ceb.2008.03.019
Smith E, Lin C, Shilatifard A. The super elongation complex (SEC) and MLL in development and disease. Genes Dev. 2011;25:661–72.
pubmed: 21460034
pmcid: 3070929
doi: 10.1101/gad.2015411
Ding Y, Zhang B, Payne JL, Song C, Ge Z, Gowda C, et al. Ikaros tumor suppressor function includes induction of active enhancers and super-enhancers along with pioneering activity. Leukemia. 2019;33:2720–31.
pubmed: 31073152
pmcid: 6842075
doi: 10.1038/s41375-019-0474-0
Zaret KS. Pioneer transcription factors initiating gene network changes. Annu Rev Genet. 2020;54:367–85.
pubmed: 32886547
pmcid: 7900943
doi: 10.1146/annurev-genet-030220-015007
Adelman K, Lis JT. Promoter-proximal pausing of RNA polymerase II: emerging roles in metazoans. Nat Rev Genet. 2012;13:720–31.
pubmed: 22986266
pmcid: 3552498
doi: 10.1038/nrg3293
Core LJ, Waterfall JJ, Gilchrist DA, Fargo DC, Kwak H, Adelman K, et al. Defining the status of RNA polymerase at promoters. Cell Rep. 2012;2:1025–35.
pubmed: 23062713
pmcid: 3483431
doi: 10.1016/j.celrep.2012.08.034
Romano G, Giordano A. Role of the cyclin-dependent kinase 9-related pathway in mammalian gene expression and human diseases. Cell Cycle. 2008;7:3664–8.
pubmed: 19029809
doi: 10.4161/cc.7.23.7122
Saunders A, Core LJ, Lis JT. Breaking barriers to transcription elongation. Nat Rev Mol Cell Biol. 2006;7:557–67.
pubmed: 16936696
doi: 10.1038/nrm1981
Zhou Q, Li T, Price DH. RNA polymerase II elongation control. Annu Rev Biochem. 2012;81:119–43.
pubmed: 22404626
pmcid: 4273853
doi: 10.1146/annurev-biochem-052610-095910
Krueger BJ, Varzavand K, Cooper JJ, Price DH. The mechanism of release of P-TEFb and HEXIM1 from the 7SK snRNP by viral and cellular activators includes a conformational change in 7SK. PLoS One. 2010;5:e12335.
pubmed: 20808803
pmcid: 2925947
doi: 10.1371/journal.pone.0012335
Li Q, Price JP, Byers SA, Cheng D, Peng J, Price DH. Analysis of the large inactive P-TEFb complex indicates that it contains one 7SK molecule, a dimer of HEXIM1 or HEXIM2, and two P-TEFb molecules containing Cdk9 phosphorylated at threonine 186. J Biol Chem. 2005;280:28819–26.
pubmed: 15965233
doi: 10.1074/jbc.M502712200
Michels AA, Fraldi A, Li Q, Adamson TE, Bonnet F, Nguyen VT, et al. Binding of the 7SK snRNA turns the HEXIM1 protein into a P-TEFb (CDK9/cyclin T) inhibitor. EMBO J. 2004;23:2608–19.
pubmed: 15201869
pmcid: 449783
doi: 10.1038/sj.emboj.7600275
Yik JH, Chen R, Nishimura R, Jennings JL, Link AJ, Zhou Q. Inhibition of P-TEFb (CDK9/Cyclin T) kinase and RNA polymerase II transcription by the coordinated actions of HEXIM1 and 7SK snRNA. Mol Cell. 2003;12:971–82.
pubmed: 14580347
doi: 10.1016/S1097-2765(03)00388-5
Chen R, Liu M, Li H, Xue Y, Ramey WN, He N, et al. PP2B and PP1alpha cooperatively disrupt 7SK snRNP to release P-TEFb for transcription in response to Ca2+ signaling. Genes Dev. 2008;22:1356–68.
pubmed: 18483222
pmcid: 2377190
doi: 10.1101/gad.1636008
Diribarne G, Bensaude O. 7SK RNA, a non-coding RNA regulating P-TEFb, a general transcription factor. RNA Biol. 2009;6:122–8.
pubmed: 19246988
doi: 10.4161/rna.6.2.8115
Popescu M, Gurel Z, Ronni T, Song C, Hung KY, Payne KJ, et al. Ikaros stability and pericentromeric localization are regulated by protein phosphatase 1. J Biol Chem. 2009;284:13869–80.
pubmed: 19282287
pmcid: 2679487
doi: 10.1074/jbc.M900209200
Orphanides G, LeRoy G, Chang CH, Luse DS, Reinberg DFACT. a factor that facilitates transcript elongation through nucleosomes. Cell. 1998;92:105–16.
pubmed: 9489704
doi: 10.1016/S0092-8674(00)80903-4
Murawska M, Brehm A. CHD chromatin remodelers and the transcription cycle. Transcription. 2011;2:244–53.
pubmed: 22223048
pmcid: 3265784
doi: 10.4161/trns.2.6.17840
Venkatesh S, Smolle M, Li H, Gogol MM, Saint M, Kumar S, et al. Set2 methylation of histone H3 lysine 36 suppresses histone exchange on transcribed genes. Nature. 2012;489:452–5.
pubmed: 22914091
doi: 10.1038/nature11326
Carrozza MJ, Li B, Florens L, Suganuma T, Swanson SK, Lee KK, et al. Histone H3 methylation by Set2 directs deacetylation of coding regions by Rpd3S to suppress spurious intragenic transcription. Cell. 2005;123:581–92.
pubmed: 16286007
doi: 10.1016/j.cell.2005.10.023
Li B, Gogol M, Carey M, Pattenden SG, Seidel C, Workman JL. Infrequently transcribed long genes depend on the Set2/Rpd3S pathway for accurate transcription. Genes Dev. 2007;21:1422–30.
pubmed: 17545470
pmcid: 1877753
doi: 10.1101/gad.1539307
Hornbeck PV, Zhang B, Murray B, Kornhauser JM, Latham V. Skrzypek E. PhosphoSitePlus, 2014: mutations, PTMs and recalibrations. Nucleic Acids Res. 2015;43:D512–20.
pubmed: 25514926
doi: 10.1093/nar/gku1267
Gomez-del Arco P, Koipally J, Georgopoulos K. Ikaros SUMOylation: switching out of repression. Mol Cell Biol. 2005;25:2688–97.
pubmed: 15767674
pmcid: 1061640
doi: 10.1128/MCB.25.7.2688-2697.2005
Apostolov A, Litim-Mecheri I, Oravecz A, Goepp M, Kirstetter P, Marchal P, et al. Sumoylation inhibits the growth suppressive properties of Ikaros. PLoS One. 2016;11:e0157767.
pubmed: 27315244
pmcid: 4912065
doi: 10.1371/journal.pone.0157767
Brown KE, Guest SS, Smale ST, Hahm K, Merkenschlager M, Fisher AG. Association of transcriptionally silent genes with Ikaros complexes at centromeric heterochromatin. Cell. 1997;91:845–54.
pubmed: 9413993
doi: 10.1016/S0092-8674(00)80472-9
Li Z, Song C, Ouyang H, Lai L, Payne KJ, Dovat S. Cell cycle-specific function of Ikaros in human leukemia. Pediatr Blood Cancer. 2012;59:69–76.
pubmed: 22106042
doi: 10.1002/pbc.23406
Dovat S, Ronni T, Russell D, Ferrini R, Cobb BS, Smale ST. A common mechanism for mitotic inactivation of C2H2 zinc finger DNA-binding domains. Genes Dev. 2002;16:2985–90.
pubmed: 12464629
pmcid: 187490
doi: 10.1101/gad.1040502
Gomez-del Arco P, Maki K, Georgopoulos K. Phosphorylation controls Ikaros’s ability to negatively regulate the G(1)-S transition. Mol Cell Biol. 2004;24:2797–807.
pubmed: 15024069
doi: 10.1128/MCB.24.7.2797-2807.2004
Gurel Z, Ronni T, Ho S, Kuchar J, Payne KJ, Turk CW, et al. Recruitment of ikaros to pericentromeric heterochromatin is regulated by phosphorylation. J Biol Chem. 2008;283:8291–300.
pubmed: 18223295
pmcid: 2276389
doi: 10.1074/jbc.M707906200
Ma H, Qazi S, Ozer Z, Zhang J, Ishkhanian R, Uckun FM. Regulatory phosphorylation of Ikaros by Bruton’s tyrosine kinase. PLoS One. 2013;8:e71302.
pubmed: 23977012
pmcid: 3747153
doi: 10.1371/journal.pone.0071302
Uckun FM, Ma H, Zhang J, Ozer Z, Dovat S, Mao C, et al. Serine phosphorylation by SYK is critical for nuclear localization and transcription factor function of Ikaros. Proc Natl Acad Sci USA. 2012;109:18072–7.
pubmed: 23071339
pmcid: 3497833
doi: 10.1073/pnas.1209828109
Ito T, Ando H, Suzuki T, Ogura T, Hotta K, Imamura Y, et al. Identification of a primary target of thalidomide teratogenicity. Science. 2010;327:1345–50.
pubmed: 20223979
doi: 10.1126/science.1177319
Gandhi AK, Kang J, Havens CG, Conklin T, Ning Y, Wu L, et al. Immunomodulatory agents lenalidomide and pomalidomide co-stimulate T cells by inducing degradation of T cell repressors Ikaros and Aiolos via modulation of the E3 ubiquitin ligase complex CRL4(CRBN.). Br J Haematol. 2014;164:811–21.
pubmed: 24328678
doi: 10.1111/bjh.12708
Kronke J, Udeshi ND, Narla A, Grauman P, Hurst SN, McConkey M, et al. Lenalidomide causes selective degradation of IKZF1 and IKZF3 in multiple myeloma cells. Science. 2014;343:301–5.
pubmed: 24292625
doi: 10.1126/science.1244851
Lu G, Middleton RE, Sun H, Naniong M, Ott CJ, Mitsiades CS, et al. The myeloma drug lenalidomide promotes the cereblon-dependent destruction of Ikaros proteins. Science. 2014;343:305–9.
pubmed: 24292623
doi: 10.1126/science.1244917
Bjorklund CC, Lu L, Kang J, Hagner PR, Havens CG, Amatangelo M, et al. Rate of CRL4(CRBN) substrate Ikaros and Aiolos degradation underlies differential activity of lenalidomide and pomalidomide in multiple myeloma cells by regulation of c-Myc and IRF4. Blood. Cancer J. 2015;5:e354.
Shi CX, Kortum KM, Zhu YX, Jedlowski P, Bruins L, Braggio E, et al. Proteasome inhibitors block Ikaros degradation by lenalidomide in multiple myeloma. Haematologica. 2015;100:e315–7.
pubmed: 25975838
pmcid: 5004433
Fecteau JF, Corral LG, Ghia EM, Gaidarova S, Futalan D, Bharati IS, et al. Lenalidomide inhibits the proliferation of CLL cells via a cereblon/p21(WAF1/Cip1)-dependent mechanism independent of functional p53. Blood. 2014;124:1637–44.
pubmed: 24990888
pmcid: 4155272
doi: 10.1182/blood-2014-03-559591
Ge Z, Song C, Ding Y, Tan BH, Desai D, Sharma A, et al. Dual targeting of MTOR as a novel therapeutic approach for high-risk B-cell acute lymphoblastic leukemia. Leukemia. 2021;35:1267–78.
pubmed: 33531656
pmcid: 8102195
doi: 10.1038/s41375-021-01132-5
Hagner PR, Chiu H, Chopra VS, Colombo M, Patel N, Estevez MO, et al. Interactome of Aiolos/Ikaros Reveals Combination Rationale of Cereblon Modulators with HDAC Inhibitors in DLBCL. Clin Cancer Res. 2022;28:3367–77.
pubmed: 35583604
pmcid: 9662945
doi: 10.1158/1078-0432.CCR-21-3347
Sanchez-Luis E, Joaquin-Garcia A, Campos-Laborie FJ, Sanchez-Guijo F, Rivas JL. Deciphering master gene regulators and associated networks of human mesenchymal stromal cells. Biomolecules. 2020;10:557.
Van Dessel N, Beke L, Gornemann J, Minnebo N, Beullens M, Tanuma N, et al. The phosphatase interactor NIPP1 regulates the occupancy of the histone methyltransferase EZH2 at Polycomb targets. Nucleic Acids Res. 2010;38:7500–12.
pubmed: 20671031
pmcid: 2995064
doi: 10.1093/nar/gkq643
Hammond-Martel I, Yu H, Affar EB. Roles of ubiquitin signaling in transcription regulation. Cell Signal. 2012;24:410–21.
pubmed: 22033037
doi: 10.1016/j.cellsig.2011.10.009
Francis OL, Payne JL, Su RJ, Payne KJ. Regulator of myeloid differentiation and function: the secret life of Ikaros. World J Biol Chem. 2011;2:119–25.
pubmed: 21765977
pmcid: 3135858
doi: 10.4331/wjbc.v2.i6.119
Tate JG, Bamford S, Jubb HC, Sondka Z, Beare DM, Bindal N, et al. COSMIC: the catalogue of somatic mutations in cancer. Nucleic Acids Res. 2019;47:D941–D7.
pubmed: 30371878
doi: 10.1093/nar/gky1015
Groth DJ, Lakkaraja MM, Ferreira JO, Feuille EJ, Bassetti JA, Kaicker SM. Management of chronic immune thrombocytopenia and presumed autoimmune hepatitis in a child with IKAROS haploinsufficiency. J Clin Immunol. 2020;40:653–7.
pubmed: 32319000
doi: 10.1007/s10875-020-00781-y
Lu G, Weng S, Matyskiela M, Zheng X, Fang W, Wood S, et al. UBE2G1 governs the destruction of cereblon neomorphic substrates. Elife. 2018;7:e40958.
pubmed: 30234487
pmcid: 6185104
doi: 10.7554/eLife.40958
Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, et al. Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009;2:ra46.
pubmed: 19690332
doi: 10.1126/scisignal.2000007
Geoghegan V, Guo A, Trudgian D, Thomas B, Acuto O. Comprehensive identification of arginine methylation in primary T cells reveals regulatory roles in cell signalling. Nat Commun. 2015;6:6758.
pubmed: 25849564
doi: 10.1038/ncomms7758
Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, et al. Integrated proteomic analysis of post-translational modifications by serial enrichment. Nat Methods. 2013;10:634–7.
pubmed: 23749302
pmcid: 3943163
doi: 10.1038/nmeth.2518
Akimov V, Barrio-Hernandez I, Hansen SVF, Hallenborg P, Pedersen AK, Bekker-Jensen DB, et al. UbiSite approach for comprehensive mapping of lysine and N-terminal ubiquitination sites. Nat Struct Mol Biol. 2018;25:631–40.
pubmed: 29967540
doi: 10.1038/s41594-018-0084-y
Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, et al. Refined preparation and use of anti-diglycine remnant (K-epsilon-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments. Mol Cell Proteom. 2013;12:825–31.
doi: 10.1074/mcp.O112.027094
Giansanti P, Stokes MP, Silva JC, Scholten A, Heck AJ. Interrogating cAMP-dependent kinase signaling in Jurkat T cells via a protein kinase A targeted immune-precipitation phosphoproteomics approach. Mol Cell Proteom. 2013;12:3350–9.
doi: 10.1074/mcp.O113.028456
Weber C, Schreiber TB, Daub H. Dual phosphoproteomics and chemical proteomics analysis of erlotinib and gefitinib interference in acute myeloid leukemia cells. J Proteom. 2012;75:1343–56.
doi: 10.1016/j.jprot.2011.11.004
Trost M, Sauvageau M, Herault O, Deleris P, Pomies C, Chagraoui J, et al. Posttranslational regulation of self-renewal capacity: insights from proteome and phosphoproteome analyses of stem cell leukemia. Blood. 2012;120:e17–27.
pubmed: 22802335
doi: 10.1182/blood-2011-12-397844
Mertins P, Mani DR, Ruggles KV, Gillette MA, Clauser KR, Wang P, et al. Proteogenomics connects somatic mutations to signalling in breast cancer. Nature. 2016;534:55–62.
pubmed: 27251275
pmcid: 5102256
doi: 10.1038/nature18003
Cho SJ, Kang H, Kim MY, Lee JE, Kim SJ, Nam SY, et al. Site-specific phosphorylation of Ikaros induced by low-dose ionizing radiation regulates cell cycle progression of B lymphoblast through CK2 and AKT activation. Int J Radiat Oncol Biol Phys. 2016;94:1207–18.
pubmed: 27026320
doi: 10.1016/j.ijrobp.2016.01.008
Huttlin EL, Jedrychowski MP, Elias JE, Goswami T, Rad R, Beausoleil SA, et al. A tissue-specific atlas of mouse protein phosphorylation and expression. Cell. 2010;143:1174–89.
pubmed: 21183079
pmcid: 3035969
doi: 10.1016/j.cell.2010.12.001
Petzold G, Fischer ES, Thoma NH. Structural basis of lenalidomide-induced CK1alpha degradation by the CRL4(CRBN) ubiquitin ligase. Nature. 2016;532:127–30.
pubmed: 26909574
doi: 10.1038/nature16979