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ZNF509S1 downregulates PUMA by inhibiting p53K382 acetylation and p53-DNA binding

Authors
 Bu-Nam Jeon  ;  Jae-Hyeon Yoon  ;  Dohyun Han  ;  Min-Kyeong Kim  ;  Youngsoo Kim  ;  Seo-Hyun Choi  ;  Jiyang Song  ;  Kyung-Sup Kim  ;  Kunhong Kim  ;  Man-Wook Hur 
Citation
 BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS, Vol.1860(9) : 962-972, 2017 
Journal Title
 BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS 
ISSN
 1874-9399 
Issue Date
2017
MeSH
Acetylation ; Animals ; Apoptosis/physiology ; Apoptosis Regulatory Proteins/metabolism ; Cell Line ; Cell Line, Tumor ; Cell Proliferation/physiology ; Cyclin-Dependent Kinase Inhibitor p21/metabolism ; DNA/metabolism* ; DNA Damage/physiology ; DNA-Binding Proteins/metabolism* ; Down-Regulation/physiology* ; E1A-Associated p300 Protein ; HCT116 Cells ; HEK293 Cells ; Humans ; Promoter Regions, Genetic/physiology ; Protein Binding/physiology ; Protein Processing, Post-Translational/physiology ; Puma/metabolism* ; Transcriptional Activation/physiology ; Tumor Suppressor Protein p53/metabolism* ; Zinc Fingers/physiology
Keywords
Apoptosis ; PUMA ; Post-translational modification ; ZNF509S1 (ZBTB49) ; p53
Abstract
Expression of the POK family protein ZNF509L, and -its S1 isoform, is induced by p53 upon exposure to genotoxic stress. Due to alternative splicing of the ZNF509 primary transcript, ZNF509S1 lacks the 6 zinc-fingers and C-terminus of ZNF509L, resulting in only one zinc-finger. ZNF509L and -S1 inhibit cell proliferation by activating p21/CDKN1A and RB transcription, respectively. When cells are exposed to severe DNA damage, p53 activates PUMA (p53-upregulated modulator of apoptosis) transcription. Interestingly, apoptosis due to transcriptional activation of PUMA by p53 is attenuated by ZNF509S1. Thus we investigated the molecular mechanism(s) underlying the transcriptional attenuation and anti-apoptotic effects of ZNF509S1. We show that ZNF509S1 modulation of p53 activity is important in PUMA gene transcription by modulating post-translational modification of p53 by p300. ZNF509S1 directly interacts with p53 and inhibits p300-mediated acetylation of p53 lysine K382, with deacetylation of p53 K382 leading to decreased DNA binding at the p53 response element 1 of the PUMA promoter. ZNF509S1 may play a role not only in cell cycle arrest, by activating RB expression, but also in rescuing cells from apoptotic death by repressing PUMA expression in cells exposed to severe DNA damage.
Full Text
https://www.sciencedirect.com/science/article/pii/S1874939917300962
DOI
10.1016/j.bbagrm.2017.07.008
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Kun Hong(김건홍) ORCID logo https://orcid.org/0000-0001-5639-6372
Kim, Kyung Sup(김경섭) ORCID logo https://orcid.org/0000-0001-8483-8537
Jeon, Bu Nam(전부남)
Hur, Man Wook(허만욱) ORCID logo https://orcid.org/0000-0002-3416-1334
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/160602
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