Aryl Hydrocarbon Receptor Interacting Protein Maintains Germinal Center B Cells through Suppression of BCL6 Degradation.
Adult
Aged
Aged, 80 and over
Animals
B-Lymphocytes
/ immunology
F-Box Proteins
/ metabolism
Female
Germinal Center
/ cytology
HEK293 Cells
Humans
Intracellular Signaling Peptides and Proteins
/ genetics
Lymphoma, Large B-Cell, Diffuse
/ immunology
Male
Mice
Middle Aged
Proteasome Endopeptidase Complex
/ metabolism
Protein Binding
Protein-Arginine N-Methyltransferases
/ metabolism
Proteolysis
Proto-Oncogene Proteins c-bcl-6
/ metabolism
Ubiquitin Thiolesterase
/ metabolism
Ubiquitination
AIP
BCL6
FBXO11
UCHL1
lymphoma
ubiquitination
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
30 04 2019
30 04 2019
Historique:
received:
15
03
2018
revised:
03
07
2018
accepted:
28
03
2019
entrez:
3
5
2019
pubmed:
3
5
2019
medline:
7
7
2020
Statut:
ppublish
Résumé
B cell lymphoma-6 (BCL6) is highly expressed in germinal center B cells, but how its expression is maintained is still not completely clear. Aryl hydrocarbon receptor interacting protein (AIP) is a co-chaperone of heat shock protein 90. Deletion of Aip in B cells decreased BCL6 expression, reducing germinal center B cells and diminishing adaptive immune responses. AIP was required for optimal AKT signaling in response to B cell receptor stimulation, and AIP protected BCL6 from ubiquitin-mediated proteasomal degradation by the E3-ubiquitin ligase FBXO11 by binding to the deubiquitinase UCHL1, thus helping to maintain the expression of BCL6. AIP was highly expressed in primary diffuse large B cell lymphomas compared to healthy tissue and other tumors. Our findings describe AIP as a positive regulator of BCL6 expression with implications for the pathobiology of diffuse large B cell lymphoma.
Identifiants
pubmed: 31042473
pii: S2211-1247(19)30469-3
doi: 10.1016/j.celrep.2019.04.014
pmc: PMC6506688
pii:
doi:
Substances chimiques
BCL6 protein, human
0
F-Box Proteins
0
Intracellular Signaling Peptides and Proteins
0
Proto-Oncogene Proteins c-bcl-6
0
UCHL1 protein, human
0
aryl hydrocarbon receptor-interacting protein
0
FBXO11 protein, human
EC 2.1.1.319
Protein-Arginine N-Methyltransferases
EC 2.1.1.319
Ubiquitin Thiolesterase
EC 3.4.19.12
Proteasome Endopeptidase Complex
EC 3.4.25.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1461-1471.e4Subventions
Organisme : Versus Arthritis
ID : 19867
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/M023230/1
Pays : United Kingdom
Organisme : Arthritis Research UK
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/M018539/1
Pays : United Kingdom
Informations de copyright
Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.
Références
Nat Med. 2009 Dec;15(12):1369-76
pubmed: 19966776
Blood. 2010 Jul 8;116(1):45-53
pubmed: 20351313
J Exp Med. 2010 Jun 7;207(6):1209-21
pubmed: 20498019
Nat Immunol. 2007 Oct;8(10):1132-9
pubmed: 17828269
Nat Rev Immunol. 2015 Mar;15(3):172-84
pubmed: 25712152
Blood. 2016 Feb 18;127(7):858-68
pubmed: 26603836
Nature. 2012 Jan 5;481(7379):90-3
pubmed: 22113614
J Biol Chem. 2000 Dec 29;275(52):41317-24
pubmed: 11013261
Nature. 2008 May 1;453(7191):106-9
pubmed: 18362914
Science. 1997 Apr 25;276(5312):589-92
pubmed: 9110977
J Clin Endocrinol Metab. 2008 Jun;93(6):2390-401
pubmed: 18381572
Immunity. 2015 Dec 15;43(6):1064-74
pubmed: 26620759
Nat Rev Cancer. 2005 Oct;5(10):761-72
pubmed: 16175177
PLoS One. 2014 Mar 07;9(3):e90054
pubmed: 24608665
J Endocrinol. 2011 Aug;210(2):137-55
pubmed: 21454441
Blood. 2016 Aug 4;128(5):660-6
pubmed: 27166359
Cell. 2011 Oct 28;147(3):629-40
pubmed: 21999944
Nat Rev Mol Cell Biol. 2017 Jun;18(6):345-360
pubmed: 28429788
Cell Rep. 2015 Dec 15;13(10):2159-73
pubmed: 26628369
Eur J Immunol. 1999 Apr;29(4):1314-23
pubmed: 10229099
Science. 2006 May 26;312(5777):1228-30
pubmed: 16728643
Proc Natl Acad Sci U S A. 1993 Jun 1;90(11):5262-6
pubmed: 8506375
Leukemia. 2010 Sep;24(9):1641-55
pubmed: 20574456
Annu Rev Immunol. 2014;32:403-32
pubmed: 24655296
Nat Rev Mol Cell Biol. 2009 Aug;10(8):550-63
pubmed: 19626045
Genes Dev. 1998 Jul 1;12(13):1953-61
pubmed: 9649500
FEBS J. 2012 Feb;279(4):532-42
pubmed: 22177318
Cell Rep. 2017 Feb 14;18(7):1687-1698
pubmed: 28199841
EMBO J. 2017 Jan 4;36(1):116-128
pubmed: 27875245
Annu Rev Immunol. 2012;30:429-57
pubmed: 22224772
Nat Immunol. 2012 Nov;13(11):1092-100
pubmed: 23001146
Immunity. 2016 Sep 20;45(3):497-512
pubmed: 27637145
Cancer Discov. 2012 May;2(5):401-4
pubmed: 22588877
Clin Cancer Res. 2016 Oct 15;22(20):5030-5042
pubmed: 27742789
Immunity. 2007 Aug;27(2):190-202
pubmed: 17723214
Immunity. 2016 Sep 20;45(3):471-482
pubmed: 27653600
Cell. 2014 Jul 17;158(2):434-448
pubmed: 25036637
Nat Chem Biol. 2013 May;9(5):307-12
pubmed: 23502424
J Clin Endocrinol Metab. 2016 Aug;101(8):3144-54
pubmed: 27253664
Biochemistry. 2007 Jan 16;46(2):610-21
pubmed: 17209571
J Exp Med. 2012 Feb 13;209(2):259-73
pubmed: 22271575
Elife. 2016 Oct 18;5:
pubmed: 27751231
Nat Rev Cancer. 2010 Aug;10(8):537-49
pubmed: 20651736
Nat Immunol. 2010 Mar;11(3):265-72
pubmed: 20139987
J Exp Med. 2017 Jan;214(1):197-208
pubmed: 28011866
Blood. 2016 Mar 24;127(12):1564-74
pubmed: 26702068
J Biol Chem. 2003 Sep 19;278(38):35878-88
pubmed: 12837759
Biochemistry. 1999 Jul 13;38(28):8907-17
pubmed: 10413464
Proc Natl Acad Sci U S A. 2000 Sep 26;97(20):10832-7
pubmed: 10995457
Nat Rev Mol Cell Biol. 2010 Jul;11(7):515-28
pubmed: 20531426
Immunity. 2015 Dec 15;43(6):1075-86
pubmed: 26620760
Nat Immunol. 2013 Apr;14(4):380-8
pubmed: 23455674
Oncogene. 2013 Mar 7;32(10):1284-95
pubmed: 22543587
Nat Protoc. 2009;4(4):495-505
pubmed: 19300443
Cell. 2010 Nov 12;143(4):592-605
pubmed: 21074050
J Biol Chem. 2014 Feb 7;289(6):3510-7
pubmed: 24356957
Nat Genet. 1997 Jun;16(2):161-70
pubmed: 9171827