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Role of Promyelocytic Leukemia Zinc Finger (PLZF) in Cell Proliferation and Cyclin-dependent Kinase Inhibitor 1A (p21WAF/CDKN1A) Gene Repression

Authors
 Won-Il Choi  ;  Min-Young Kim  ;  Bu-Nam Jeon  ;  Dong-In Koh  ;  Chae-Ok Yun  ;  Yan Li  ;  Choong-Eun Lee  ;  Jiyoung Oh  ;  Kunhong Kim  ;  Man-Wook Hur 
Citation
 JOURNAL OF BIOLOGICAL CHEMISTRY, Vol.289(27) : 18625-18640, 2014 
Journal Title
 JOURNAL OF BIOLOGICAL CHEMISTRY 
ISSN
 0021-9258 
Issue Date
2014
MeSH
Acetylation ; Animals ; Cell Line, Tumor ; Cell Proliferation ; Cell Transformation, Neoplastic ; Cyclin-Dependent Kinase Inhibitor p21/genetics* ; Gene Expression Regulation, Neoplastic* ; Gene Knockdown Techniques ; Histone Deacetylases/metabolism ; Histones/metabolism ; Humans ; Kruppel-Like Transcription Factors/deficiency ; Kruppel-Like Transcription Factors/genetics ; Kruppel-Like Transcription Factors/metabolism* ; Mice ; Promoter Regions, Genetic/genetics ; Promyelocytic Leukemia Zinc Finger Protein ; Repressor Proteins/deficiency ; Repressor Proteins/genetics ; Repressor Proteins/metabolism* ; Sp1 Transcription Factor/metabolism ; Transcription, Genetic ; Tumor Suppressor Protein p53/metabolism
Keywords
Cell Cycle ; PLZF ; Specificity Protein 1 (Sp1) ; Transcription Regulation ; Transcription Repressor ; p21WAF/CDKN1A ; p53
Abstract
Promyelocytic leukemia zinc finger (PLZF) is a transcription repressor that was initially isolated as a fusion protein with retinoic acid receptor α. PLZF is aberrantly overexpressed in various human solid tumors, such as clear cell renal carcinoma, glioblastoma, and seminoma. PLZF causes cellular transformation of NIH3T3 cells and increases cell proliferation in several cell types. PLZF also increases tumor growth in the mouse xenograft tumor model. PLZF may stimulate cell proliferation by controlling expression of the genes of the p53 pathway (ARF, TP53, and CDKN1A). We found that PLZF can directly repress transcription of CDKN1A encoding p21, a negative regulator of cell cycle progression. PLZF binds to the proximal Sp1-binding GC-box 5/6 and the distal p53-responsive elements of the CDKN1A promoter to repress transcription. Interestingly, PLZF interacts with Sp1 or p53 and competes with Sp1 or p53. PLZF interacts with corepressors, such as mSin3A, NCoR, and SMRT, thereby deacetylates Ac-H3 and Ac-H4 histones at the CDKN1A promoter, which indicated the involvement of the corepressor·HDACs complex in transcription repression by PLZF. Also, PLZF represses transcription of TP53 and also decreases p53 protein stability by ubiquitination. PLZF may act as a potential proto-oncoprotein in various cell types.
Full Text
http://www.jbc.org/content/289/27/18625.long
DOI
10.1074/jbc.M113.538751
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
Yonsei Authors
Kim, Kun Hong(김건홍) ORCID logo https://orcid.org/0000-0001-5639-6372
Kim, Min Young(김민영)
Jeon, Bu Nam(전부남)
Choi, Won Il(최원일)
Hur, Man Wook(허만욱) ORCID logo https://orcid.org/0000-0002-3416-1334
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/99040
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