Structural basis of histone H2A lysine 119 deubiquitination by Polycomb repressive deubiquitinase BAP1/ASXL1.
Journal
Science advances
ISSN: 2375-2548
Titre abrégé: Sci Adv
Pays: United States
ID NLM: 101653440
Informations de publication
Date de publication:
09 08 2023
09 08 2023
Historique:
medline:
11
8
2023
pubmed:
9
8
2023
entrez:
9
8
2023
Statut:
ppublish
Résumé
Histone H2A lysine 119 (H2AK119Ub) is monoubiquitinated by Polycomb repressive complex 1 and deubiquitinated by Polycomb repressive deubiquitinase complex (PR-DUB). PR-DUB cleaves H2AK119Ub to restrict focal H2AK119Ub at Polycomb target sites and to protect active genes from aberrant silencing. The PR-DUB subunits (BAP1 and ASXL1) are among the most frequently mutated epigenetic factors in human cancers. How PR-DUB establishes specificity for H2AK119Ub over other nucleosomal ubiquitination sites and how disease-associated mutations of the enzyme affect activity are unclear. Here, we determine a cryo-EM structure of human BAP1 and the ASXL1 DEUBAD in complex with a H2AK119Ub nucleosome. Our structural, biochemical, and cellular data reveal the molecular interactions of BAP1 and ASXL1 with histones and DNA that are critical for restructuring the nucleosome and thus establishing specificity for H2AK119Ub. These results further provide a molecular explanation for how >50 mutations in BAP1 and ASXL1 found in cancer can dysregulate H2AK119Ub deubiquitination, providing insight into understanding cancer etiology.
Identifiants
pubmed: 37556531
doi: 10.1126/sciadv.adg9832
pmc: PMC10411902
doi:
Substances chimiques
Histones
0
Nucleosomes
0
Lysine
K3Z4F929H6
Ubiquitin Thiolesterase
EC 3.4.19.12
Polycomb-Group Proteins
0
Drosophila Proteins
0
ASXL1 protein, human
0
Repressor Proteins
0
BAP1 protein, human
0
Tumor Suppressor Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
eadg9832Subventions
Organisme : NCI NIH HHS
ID : R01 CA266978
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM115882
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM138181
Pays : United States
Organisme : NIGMS NIH HHS
ID : R44 GM119893
Pays : United States
Commentaires et corrections
Type : UpdateOf
Références
Clin Cancer Res. 2015 Mar 15;21(6):1447-56
pubmed: 25589618
Nat Commun. 2022 Jul 23;13(1):4264
pubmed: 35871175
Cancer Res. 2014 Aug 15;74(16):4282-94
pubmed: 24894717
Nat Rev Genet. 2007 Jan;8(1):9-22
pubmed: 17173055
Nat Cancer. 2020 Apr;1(4):452-468
pubmed: 35121966
Nat Cancer. 2021 May;2(5):515-526
pubmed: 35122023
Sci Adv. 2019 Sep 18;5(9):eaax1738
pubmed: 31555735
J Clin Invest. 2019 Oct 1;129(10):4276-4289
pubmed: 31483290
Science. 2018 Feb 16;359(6377):801-806
pubmed: 29301960
Protein Sci. 2021 Jan;30(1):136-150
pubmed: 33030237
Nat Methods. 2019 Aug;16(8):771-777
pubmed: 31308549
Methods Enzymol. 2010;481:109-26
pubmed: 20887855
Cell. 2019 Mar 7;176(6):1490-1501.e12
pubmed: 30765112
DNA Repair (Amst). 2015 Dec;36:36-42
pubmed: 26422137
Nat Commun. 2020 Apr 24;11(1):1975
pubmed: 32332851
Genes Dev. 2021 May 1;35(9-10):749-770
pubmed: 33888563
Cell. 2020 Dec 23;183(7):1962-1985.e31
pubmed: 33242424
Nucleic Acids Res. 2020 Sep 25;48(17):9415-9432
pubmed: 32658293
N Engl J Med. 2017 Jun 1;376(22):2109-2121
pubmed: 28445112
J Comput Chem. 2004 Oct;25(13):1605-12
pubmed: 15264254
J Struct Biol. 2016 Jan;193(1):1-12
pubmed: 26592709
Nat Methods. 2017 Mar;14(3):290-296
pubmed: 28165473
J Am Chem Soc. 2022 Feb 9;144(5):2284-2291
pubmed: 35081309
Nat Commun. 2016 May 10;7:11479
pubmed: 27161491
Bioinformatics. 2012 Aug 1;28(15):1953-6
pubmed: 22645167
Biochem Soc Trans. 2021 Jun 30;49(3):1041-1054
pubmed: 34156443
Oncotarget. 2016 Jan 26;7(4):4624-31
pubmed: 26683228
Annu Rev Biochem. 2012;81:203-29
pubmed: 22524316
Nat Struct Mol Biol. 2022 May;29(5):493-501
pubmed: 35581345
Nature. 2019 Dec;576(7785):112-120
pubmed: 31748746
Nat Med. 2017 Jun;23(6):703-713
pubmed: 28481359
Cancer Res. 2018 Mar 1;78(5):1200-1213
pubmed: 29284740
Science. 2021 Jan 22;371(6527):
pubmed: 33479126
Methods Enzymol. 2004;375:23-44
pubmed: 14870657
IUCrJ. 2019 Jan 01;6(Pt 1):5-17
pubmed: 30713699
Nat Commun. 2022 Nov 4;13(1):6658
pubmed: 36333289
Cancer Discov. 2020 Aug;10(8):1103-1120
pubmed: 32690542
Elife. 2020 Jan 10;9:
pubmed: 31922488
Mol Cell. 2015 Mar 5;57(5):887-900
pubmed: 25702870
Nature. 2020 Feb;578(7793):82-93
pubmed: 32025007
Science. 2011 Nov 18;334(6058):977-82
pubmed: 22096199
Nature. 2016 Aug 4;536(7614):100-3
pubmed: 27462807
Nat Genet. 2014 Jun;46(6):583-7
pubmed: 24816255
Eur Urol. 2015 Dec;68(6):970-7
pubmed: 26278805
Protein Sci. 2021 Jan;30(1):70-82
pubmed: 32881101
Cancer Discov. 2017 Oct;7(10):1116-1135
pubmed: 28667006
Cancer Discov. 2012 May;2(5):401-4
pubmed: 22588877
Genes Dev. 2022 Oct 1;36(19-20):1046-1061
pubmed: 36357125
Nat Genet. 2013 Aug;45(8):860-7
pubmed: 23797736
Eur Urol. 2018 Mar;73(3):322-339
pubmed: 28927585
Stem Cell Reports. 2019 May 14;12(5):861-868
pubmed: 31006630
Nat Methods. 2013 Jun;10(6):584-90
pubmed: 23644547
Nat Methods. 2021 Mar;18(3):303-308
pubmed: 33589837
Transl Lung Cancer Res. 2017 Jun;6(3):270-278
pubmed: 28713672
Mod Pathol. 2015 Aug;28(8):1043-57
pubmed: 26022455
Nat Commun. 2016 Jan 07;7:10292
pubmed: 26739236
Acta Crystallogr D Biol Crystallogr. 2004 Dec;60(Pt 12 Pt 1):2126-32
pubmed: 15572765
Nature. 2014 Oct 30;514(7524):591-6
pubmed: 25355358
Transl Vis Sci Technol. 2019 May 06;8(3):11
pubmed: 31110912
Nature. 2010 Sep 30;467(7315):562-6
pubmed: 20739938
Science. 2021 Jan 22;371(6527):
pubmed: 33479123
Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):213-21
pubmed: 20124702
Nat Genet. 2015 May;47(5):505-511
pubmed: 25822088
Mol Cell. 2021 Sep 2;81(17):3526-3541.e8
pubmed: 34186021
Elife. 2018 Nov 09;7:
pubmed: 30412051
Cancer Res. 2015 Jan 15;75(2):264-9
pubmed: 25488749
Nat Commun. 2019 Jan 21;10(1):348
pubmed: 30664650
J Mol Biol. 2002 Jun 21;319(5):1097-113
pubmed: 12079350
Structure. 2019 Mar 5;27(3):528-536.e4
pubmed: 30639226
Nature. 2018 Feb 8;554(7691):189-194
pubmed: 29420467
Nat Genet. 2012 Sep;44(9):1006-14
pubmed: 22842228
J Exp Med. 2013 Nov 18;210(12):2641-59
pubmed: 24218140
Blood. 2018 Jan 18;131(3):328-341
pubmed: 29113963
Nat Med. 2018 Jun;24(6):758-769
pubmed: 29785026
Cell. 2018 Apr 5;173(2):291-304.e6
pubmed: 29625048
Curr Opin Struct Biol. 2016 Apr;37:54-61
pubmed: 26764865
Nat Commun. 2018 Sep 26;9(1):3932
pubmed: 30258054
Sci Signal. 2013 Apr 02;6(269):pl1
pubmed: 23550210
Nat Methods. 2017 Apr;14(4):331-332
pubmed: 28250466
PLoS One. 2019 Feb 4;14(2):e0211507
pubmed: 30716094
Cell. 2019 May 2;177(4):1035-1049.e19
pubmed: 31031003
Methods. 2014 Dec;70(2-3):134-8
pubmed: 25063569
Clin Cancer Res. 2022 Oct 3;28(19):4302-4311
pubmed: 35849120
Cell Death Discov. 2021 Jan 22;7(1):20
pubmed: 33483476
Eur Urol. 2015 Feb;67(2):198-201
pubmed: 25092538
Mol Cell. 2019 Jun 6;74(5):1010-1019.e6
pubmed: 30981630
Mol Cell. 2021 Jan 7;81(1):166-182.e6
pubmed: 33238161
Org Biomol Chem. 2016 Jan 21;14(3):835-9
pubmed: 26615908
Nat Commun. 2021 Jan 29;12(1):714
pubmed: 33514705
Cancer Cell. 2019 Jun 10;35(6):932-947.e8
pubmed: 31130341
Nature. 2010 May 13;465(7295):243-7
pubmed: 20436459
Nature. 2012 Apr 18;486(7403):346-52
pubmed: 22522925
Science. 2006 Feb 10;311(5762):856-61
pubmed: 16469929
Nature. 2023 Apr;616(7955):176-182
pubmed: 36991118