VPRBP Functions Downstream of the Androgen Receptor and OGT to Restrict p53 Activation in Prostate Cancer.
Journal
Molecular cancer research : MCR
ISSN: 1557-3125
Titre abrégé: Mol Cancer Res
Pays: United States
ID NLM: 101150042
Informations de publication
Date de publication:
06 07 2022
06 07 2022
Historique:
received:
30
06
2021
revised:
13
02
2022
accepted:
23
03
2022
pubmed:
30
3
2022
medline:
9
7
2022
entrez:
29
3
2022
Statut:
ppublish
Résumé
Androgen receptor (AR) is a major driver of prostate cancer initiation and progression. O-GlcNAc transferase (OGT), the enzyme that catalyzes the covalent addition of UDP-N-acetylglucosamine (UDP-GlcNAc) to serine and threonine residues of proteins, is often highly expressed in prostate cancer with its expression correlated with high Gleason score. In this study, we have identified an AR and OGT coregulated factor, Vpr (HIV-1) binding protein (VPRBP) also known as DDB1 and CUL4 Associated Factor 1 (DCAF1). We show that VPRBP is regulated by the AR at the transcript level, and stabilized by OGT at the protein level. VPRBP knockdown in prostate cancer cells led to a significant decrease in cell proliferation, p53 stabilization, nucleolar fragmentation, and increased p53 recruitment to the chromatin. In human prostate tumor samples, VPRBP protein overexpression correlated with AR amplification, OGT overexpression, a shorter time to postoperative biochemical progression and poor clinical outcome. In clinical transcriptomic data, VPRBP expression was positively correlated with the AR and also with AR activity gene signatures. In conclusion, we have shown that VPRBP/DCAF1 promotes prostate cancer cell proliferation by restraining p53 activation under the influence of the AR and OGT.
Identifiants
pubmed: 35348747
pii: 694065
doi: 10.1158/1541-7786.MCR-21-0477
pmc: PMC9381113
doi:
Substances chimiques
Receptors, Androgen
0
TP53 protein, human
0
Tumor Suppressor Protein p53
0
Ubiquitin-Protein Ligases
EC 2.3.2.27
N-Acetylglucosaminyltransferases
EC 2.4.1.-
OGT protein, human
EC 2.4.1.255
DCAF1 protein, human
EC 2.7.11.1
Protein Serine-Threonine Kinases
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1047-1060Informations de copyright
©2022 The Authors; Published by the American Association for Cancer Research.
Références
DNA Repair (Amst). 2016 Jun;42:63-71
pubmed: 27156098
Nat Cell Biol. 2006 Oct;8(10):1074-83
pubmed: 16964247
Oncogene. 2006 Nov 23;25(55):7311-23
pubmed: 16751804
Kidney Int Suppl. 1995 Dec;52:S14-7
pubmed: 8587275
Science. 2017 May 26;356(6340):
pubmed: 28495876
EMBO J. 1992 Nov;11(11):3995-4005
pubmed: 1396589
Prostate Cancer Prostatic Dis. 2014 Mar;17(1):18-22
pubmed: 24366413
Nat Rev Mol Cell Biol. 2017 Jul;18(7):452-465
pubmed: 28488703
Cell Cycle. 2007 Jan 15;6(2):182-8
pubmed: 17314515
Mol Cell. 2013 Nov 7;52(3):459-67
pubmed: 24140421
Oncotarget. 2015 May 20;6(14):12587-602
pubmed: 25869206
PLoS Biol. 2007 May;5(5):e123
pubmed: 17472438
Mol Med Rep. 2014 Aug;10(2):897-904
pubmed: 24865644
Genome Res. 2015 Feb;25(2):179-88
pubmed: 25391375
Oncogene. 2007 Jun 28;26(30):4453-63
pubmed: 17297473
J Mol Cell Biol. 2019 Sep 19;11(9):725-735
pubmed: 30590706
J Urol. 2006 May;175(5):1695-9; discussion 1699
pubmed: 16600733
Nat Immunol. 2016 Jun;17(6):712-20
pubmed: 27111141
Nucleic Acids Res. 2006 Jan 1;34(Database issue):D535-9
pubmed: 16381927
Bioinformatics. 2011 Jun 15;27(12):1739-40
pubmed: 21546393
EMBO J. 2011 May 20;30(13):2719-33
pubmed: 21602788
PLoS Pathog. 2010 Sep 02;6(9):e1001080
pubmed: 20824083
Nat Commun. 2016 Jan 05;7:10307
pubmed: 26728942
J Am Chem Soc. 2018 Oct 24;140(42):13542-13545
pubmed: 30285435
PLoS Genet. 2013;9(10):e1003857
pubmed: 24098154
Front Oncol. 2019 Sep 04;9:858
pubmed: 31552182
Oncogene. 2009 Dec 3;28(48):4295-305
pubmed: 19749794
Cell Rep. 2020 May 26;31(8):107669
pubmed: 32460015
BMC Biol. 2019 Jul 4;17(1):52
pubmed: 31272438
Cell Rep. 2015 Dec 29;13(12):2879-91
pubmed: 26711351
Nucleus. 2014 Sep-Oct;5(5):402-26
pubmed: 25482194
J Cell Biol. 2015 Mar 30;208(7):869-80
pubmed: 25825515
Gene. 2001 Jan 24;263(1-2):131-40
pubmed: 11223251
Nat Commun. 2015 Sep 24;6:8468
pubmed: 26399441
J Cell Sci. 1998 Dec;111 ( Pt 23):3497-506
pubmed: 9811564
Proc Natl Acad Sci U S A. 2007 Jul 10;104(28):11778-83
pubmed: 17609381
Theranostics. 2019 Apr 12;9(8):2183-2197
pubmed: 31149037
Cancer Res. 2013 Aug 15;73(16):5277-87
pubmed: 23720054
Sci Adv. 2020 Dec 18;6(51):
pubmed: 33355139
Nat Commun. 2018 Jan 2;9(1):20
pubmed: 29295995
Mol Cell Biol. 2012 Feb;32(4):783-96
pubmed: 22184063
Proc Natl Acad Sci U S A. 2002 Sep 3;99(18):11890-5
pubmed: 12185249
Proc Natl Acad Sci U S A. 2018 Jul 10;115(28):7302-7307
pubmed: 29941599
Nucleic Acids Res. 2016 Jul 27;44(13):6070-86
pubmed: 27280975
EMBO J. 1993 Feb;12(2):461-8
pubmed: 8440237
Oncol Lett. 2016 Jun;11(6):3605-3610
pubmed: 27313679
Genome Res. 2017 Oct;27(10):1645-1657
pubmed: 28904012
Curr Biol. 1997 Jun 1;7(6):375-86
pubmed: 9197238
Endocr Relat Cancer. 2017 Mar;24(3):R49-R64
pubmed: 28159857
Cell Stress. 2018 May 10;2(6):125-140
pubmed: 31225478
Cell Rep. 2017 Jun 6;19(10):2060-2073
pubmed: 28591578
Front Endocrinol (Lausanne). 2013 Aug 12;4:99
pubmed: 23964270