The BRCA1/BARD1 ubiquitin ligase and its substrates.
BRCA1 Protein
/ genetics
Breast Neoplasms
/ genetics
Carcinogenesis
/ genetics
Cell Line, Tumor
DNA Breaks, Double-Stranded
DNA Repair
Estrogen Receptor alpha
/ genetics
Female
Gene Expression Regulation, Neoplastic
Histones
/ genetics
Humans
Mutation
Neoplasm Proteins
/ genetics
Ovarian Neoplasms
/ genetics
Tumor Suppressor Proteins
/ genetics
Ubiquitin
/ genetics
Ubiquitin-Protein Ligases
/ genetics
BARD1
BRCA1
ubiquitin ligases
ubiquitin signaling
ubiquitins
Journal
The Biochemical journal
ISSN: 1470-8728
Titre abrégé: Biochem J
Pays: England
ID NLM: 2984726R
Informations de publication
Date de publication:
30 09 2021
30 09 2021
Historique:
received:
07
07
2021
revised:
03
09
2021
accepted:
07
09
2021
entrez:
30
9
2021
pubmed:
1
10
2021
medline:
25
11
2021
Statut:
ppublish
Résumé
Mutations in breast cancer type 1 susceptibility protein (BRCA1) and its heterodimeric binding partner BARD1 confer a high risk for the development of breast and ovarian cancers. The sole enzymatic function of the BRCA1/BARD1 complex is as a RING-type E3 ubiquitin (Ub) ligase, leading to the deposition of Ub signals onto a variety of substrate proteins. Distinct types of Ub signals deposited by BRCA1/BARD1 (i.e. degradative vs. non-degradative; mono-Ub vs. poly-Ub chains) on substrate proteins mediate aspects of its function in DNA double-stranded break repair, cell-cycle regulation, and transcriptional regulation. While cancer-predisposing mutations in both subunits lead to the inactivation of BRCA1/BARD1 ligase activity, controversy remains as to whether its Ub ligase activity directly inhibits tumorigenesis. Investigation of BRCA1/BARD1 substrates using rigorous, well-validated mutants and experimental systems will ultimately clarify the role of its ligase activity in cancer and possibly establish prognostic and diagnostic metrics for patients with mutations. In this review, we discuss the Ub ligase function of BRCA1/BARD1, highlighting experimental approaches, mechanistic considerations, and reagents that are useful in the study of substrate ubiquitylation. We also discuss the current understanding of two well-established BRCA1/BARD1 substrates (nucleosomal H2A and estrogen receptor α) and several recently discovered substrates (p50, NF2, Oct1, and LARP7). Lessons from the current body of work should provide a road map to researchers examining novel substrates and biological functions attributed to BRCA1/BARD1 Ub ligase activity.
Identifiants
pubmed: 34591954
pii: 229865
doi: 10.1042/BCJ20200864
pmc: PMC8763022
mid: NIHMS1767816
doi:
Substances chimiques
BRCA1 Protein
0
BRCA1 protein, human
0
ESR1 protein, human
0
Estrogen Receptor alpha
0
Histones
0
Neoplasm Proteins
0
Tumor Suppressor Proteins
0
Ubiquitin
0
BARD1 protein, human
EC 2.3.2.27
Ubiquitin-Protein Ligases
EC 2.3.2.27
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
3467-3483Subventions
Organisme : NCI NIH HHS
ID : R01 CA260834
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM088055
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM008268
Pays : United States
Organisme : NIGMS NIH HHS
ID : R15 GM135900
Pays : United States
Informations de copyright
© 2021 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.
Références
Oncotarget. 2016 Apr 12;7(15):19884-96
pubmed: 26943587
Sci Adv. 2017 Sep 20;3(9):e1701386
pubmed: 28948225
Mol Cell Biol. 2005 Oct;25(19):8656-68
pubmed: 16166645
Mol Cell Biol. 2010 Jun;30(11):2787-98
pubmed: 20351172
Mol Cell. 2021 Jul 1;81(13):2765-2777.e6
pubmed: 34102105
Mol Cell Biol. 2003 Jul;23(14):5056-63
pubmed: 12832489
FEBS J. 2015 Feb;282(4):630-46
pubmed: 25400280
Cancer Res. 2007 Dec 1;67(23):11186-94
pubmed: 18056443
Proc Natl Acad Sci U S A. 2001 Oct 9;98(21):12078-83
pubmed: 11593018
J Natl Cancer Inst. 2007 Nov 21;99(22):1683-94
pubmed: 18000219
Proc Natl Acad Sci U S A. 2003 May 13;100(10):5646-51
pubmed: 12732733
Nat Struct Mol Biol. 2007 Oct;14(10):941-8
pubmed: 17873885
Nature. 2017 Oct 19;550(7676):360-365
pubmed: 28976962
J Biol Chem. 2003 Feb 14;278(7):5255-63
pubmed: 12431996
J Biol Chem. 1999 Apr 16;274(16):11334-8
pubmed: 10196224
Hum Mol Genet. 2006 Feb 15;15(4):599-606
pubmed: 16403807
J Biol Chem. 2002 Jun 14;277(24):21315-24
pubmed: 11925436
Nat Genet. 1994 Dec;8(4):399-404
pubmed: 7894493
Biochem Biophys Res Commun. 2014 Feb 21;444(4):549-54
pubmed: 24472556
Oncogene. 2013 Oct 17;32(42):5005-16
pubmed: 23246971
J Biol Chem. 2004 Aug 6;279(32):33909-18
pubmed: 15166217
J Biol Chem. 2012 Nov 30;287(49):41014-22
pubmed: 23086937
Oncogene. 2014 Feb 6;33(6):713-723
pubmed: 23435429
Proc Natl Acad Sci U S A. 1999 Sep 28;96(20):11364-9
pubmed: 10500182
Nat Commun. 2018 Jan 15;9(1):229
pubmed: 29335415
PLoS One. 2014 Jul 10;9(7):e102438
pubmed: 25010005
Nat Commun. 2021 Feb 23;12(1):1243
pubmed: 33623049
Protein Sci. 2017 Mar;26(3):475-483
pubmed: 27977889
Am J Hum Genet. 2018 Oct 4;103(4):498-508
pubmed: 30219179
Nature. 2019 Jul;571(7766):521-527
pubmed: 31270457
Biochim Biophys Acta. 2014 Jan;1843(1):47-60
pubmed: 23747565
J Proteome Res. 2011 Nov 4;10(11):5191-8
pubmed: 21950761
Biochim Biophys Acta. 2016 Jun;1859(6):792-804
pubmed: 26877236
Nat Struct Mol Biol. 2021 Mar;28(3):268-277
pubmed: 33589814
J Biol Chem. 2004 Feb 6;279(6):3916-24
pubmed: 14638690
Hum Mol Genet. 2004 Apr 15;13(8):807-17
pubmed: 14976165
Proc Natl Acad Sci U S A. 2019 Apr 9;116(15):7363-7370
pubmed: 30918126
PLoS One. 2020 Feb 24;15(2):e0229000
pubmed: 32092106
Nat Commun. 2015 Jul 07;6:7621
pubmed: 26151332
Proc Natl Acad Sci U S A. 2008 Dec 30;105(52):20876-81
pubmed: 19088202
Cancer Res. 2014 May 15;74(10):2773-2784
pubmed: 24638981
Mol Endocrinol. 2010 Jan;24(1):76-90
pubmed: 19887647
Cancer Med. 2019 Nov;8(15):6730-6740
pubmed: 31512408
Oncogene. 2001 Jan 4;20(1):77-87
pubmed: 11244506
Mol Cell. 2010 May 14;38(3):369-82
pubmed: 20471943
Genes Dev. 2006 Jul 1;20(13):1721-6
pubmed: 16818604
J Biol Chem. 2003 Sep 12;278(37):34743-6
pubmed: 12890688
Curr Cancer Drug Targets. 2009 Jun;9(4):566-71
pubmed: 19519322
Elife. 2014 Jul 22;3:e02907
pubmed: 25053741
J Biol Chem. 2001 Nov 2;276(44):41399-406
pubmed: 11526114
Oncogene. 2004 Mar 11;23(10):1809-20
pubmed: 14647430
Comput Struct Biotechnol J. 2012 Apr 1;1(1):
pubmed: 22737296
Genes Dev. 2005 May 15;19(10):1227-37
pubmed: 15905410
Cell Rep. 2017 May 30;19(9):1758-1766
pubmed: 28564596
Mol Endocrinol. 2007 Mar;21(3):651-63
pubmed: 17185394
Cell Rep. 2014 Aug 21;8(4):999-1005
pubmed: 25131202
Nature. 2011 Sep 07;477(7363):179-84
pubmed: 21901007
Cancer Res. 2001 Nov 1;61(21):7713-8
pubmed: 11691781
J Biol Chem. 2005 Jul 1;280(26):24498-505
pubmed: 15886201
PLoS Genet. 2019 Mar 29;15(3):e1008049
pubmed: 30925164
Mol Cancer Res. 2018 Mar;16(3):439-452
pubmed: 29330289
Nat Struct Biol. 2001 Oct;8(10):833-7
pubmed: 11573085
J Biol Chem. 2002 Mar 8;277(10):8061-7
pubmed: 11777930
Nat Chem Biol. 2015 Jan;11(1):83-9
pubmed: 25436519
Cancer Res. 2007 Feb 1;67(3):951-8
pubmed: 17283126
Cancer Biol Ther. 2006 May;5(5):470-5
pubmed: 16721040
Proc Natl Acad Sci U S A. 2018 Feb 6;115(6):1316-1321
pubmed: 29367421
Breast Cancer Res. 2019 Apr 29;21(1):55
pubmed: 31036035
Proc Natl Acad Sci U S A. 2007 Apr 17;104(16):6614-9
pubmed: 17420471
Cancer Res. 2009 Feb 1;69(3):1125-34
pubmed: 19176389
Cell Res. 2016 Apr;26(4):423-40
pubmed: 27002219
Cell Div. 2008 Jan 07;3:1
pubmed: 18179693
Cell Rep. 2021 Mar 30;34(13):108921
pubmed: 33789098
Nature. 2014 Oct 30;514(7524):591-6
pubmed: 25355358
Nat Commun. 2020 Oct 6;11(1):5007
pubmed: 33024116
EMBO J. 2002 Dec 16;21(24):6755-62
pubmed: 12485996
Nat Struct Mol Biol. 2005 Jul;12(7):589-93
pubmed: 15965487
J Mol Biol. 2005 Jan 14;345(2):275-87
pubmed: 15571721
Proc Natl Acad Sci U S A. 2004 Apr 27;101(17):6484-9
pubmed: 15096610
Oncogene. 2008 Feb 14;27(8):1045-54
pubmed: 17700520
Methods Mol Biol. 2012;876:163-72
pubmed: 22576094
Annu Rev Genet. 2018 Nov 23;52:65-87
pubmed: 30183404
Cancer Res. 2005 Jan 1;65(1):6-10
pubmed: 15665273
Cell Stem Cell. 2016 Jul 7;19(1):52-65
pubmed: 27292187
Nature. 2018 Oct;562(7726):217-222
pubmed: 30209399
J Biol Chem. 2002 Jun 14;277(24):22085-92
pubmed: 11927591
Mol Cell Biol. 2004 Oct;24(19):8457-66
pubmed: 15367667
Mol Cell. 2018 Jun 7;70(5):842-853.e7
pubmed: 29861157
Cell Rep. 2020 Jul 28;32(4):107974
pubmed: 32726637
Proc Natl Acad Sci U S A. 2007 Apr 3;104(14):5794-9
pubmed: 17392432
Radiat Res. 2010 Jul;174(1):1-13
pubmed: 20681793
Methods Mol Biol. 2018;1844:19-31
pubmed: 30242700
FEBS Lett. 2011 Sep 16;585(18):2836-44
pubmed: 21570976
Lab Invest. 2012 Jul;92(7):1013-9
pubmed: 22488152
Mol Cell. 2012 Sep 28;47(6):933-42
pubmed: 22885007
Cancer Res. 2011 May 1;71(9):3422-31
pubmed: 21531767
Science. 2011 Oct 28;334(6055):525-8
pubmed: 22034435
Oncogene. 2006 Sep 25;25(43):5854-63
pubmed: 16998500
Curr Biol. 2012 Sep 25;22(18):1659-66
pubmed: 22863316
Biology (Basel). 2013 Jan 02;2(1):40-63
pubmed: 24832651
EMBO Rep. 2008 Jun;9(6):569-75
pubmed: 18483487
Cancer Biol Ther. 2006 Feb;5(2):137-41
pubmed: 16479151
Proc Natl Acad Sci U S A. 2008 May 13;105(19):7040-5
pubmed: 18443292
Environ Mol Mutagen. 2009 Oct;50(8):649-53
pubmed: 19274767
Genetics. 2015 Jun;200(2):413-22
pubmed: 25823446
Nat Rev Mol Cell Biol. 2020 May;21(5):284-299
pubmed: 32094664
Science. 1994 Oct 7;266(5182):66-71
pubmed: 7545954
Mol Cell. 2007 Dec 14;28(5):730-8
pubmed: 18082598
Biochemistry. 2005 Aug 23;44(33):10941-6
pubmed: 16101277
Nature. 2009 Dec 17;462(7275):886-90
pubmed: 20016594
Cancer Cell. 2011 Dec 13;20(6):797-809
pubmed: 22172724
Proc Natl Acad Sci U S A. 2004 Dec 7;101(49):17108-13
pubmed: 15563594
J Biol Chem. 2004 Jul 23;279(30):30919-22
pubmed: 15184379
Nat Cell Biol. 2019 Mar;21(3):311-318
pubmed: 30804502
Science. 1990 Dec 21;250(4988):1684-9
pubmed: 2270482
Science. 2003 Oct 24;302(5645):643-6
pubmed: 14576434
Cancer Biol Ther. 2008 Oct;7(10):1540-3
pubmed: 18927495
J Biol Chem. 2001 May 4;276(18):14537-40
pubmed: 11278247
Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):5134-9
pubmed: 11320250
Nucleic Acids Res. 2018 Jan 4;46(D1):D1062-D1067
pubmed: 29165669
Cancer Res. 2010 Aug 1;70(15):6384-92
pubmed: 20631078
Nat Struct Mol Biol. 2016 Jul;23(7):647-55
pubmed: 27239795
Oncogene. 2002 Oct 31;21(50):7730-9
pubmed: 12400015
IUBMB Life. 2011 Jan;63(1):49-53
pubmed: 21280177