title: Role of promyelocytic leukemia zinc finger (PLZF) in cell proliferation and cyclin-dependent kinase inhibitor 1A (p21WAF/CDKN1A) gene repression.
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.
authors.affiliation: From the Department of Biochemistry and Molecular Biology, Brain Korea 21 Plus Project for Medical Science, Severance Biomedical Research Institute, Yonsei University School of Medicine, 50 Yonsei-Ro, SeoDaeMoon-Gu, Seoul 120-752.
authors.forename: Won-Il
authors.initials: WI
authors.lastname: Choi
authors.affiliation: From the Department of Biochemistry and Molecular Biology, Brain Korea 21 Plus Project for Medical Science, Severance Biomedical Research Institute, Yonsei University School of Medicine, 50 Yonsei-Ro, SeoDaeMoon-Gu, Seoul 120-752.
authors.forename: Min-Young
authors.initials: MY
authors.lastname: Kim
authors.affiliation: From the Department of Biochemistry and Molecular Biology, Brain Korea 21 Plus Project for Medical Science, Severance Biomedical Research Institute, Yonsei University School of Medicine, 50 Yonsei-Ro, SeoDaeMoon-Gu, Seoul 120-752.
authors.forename: Bu-Nam
authors.initials: BN
authors.lastname: Jeon
authors.affiliation: From the Department of Biochemistry and Molecular Biology, Brain Korea 21 Plus Project for Medical Science, Severance Biomedical Research Institute, Yonsei University School of Medicine, 50 Yonsei-Ro, SeoDaeMoon-Gu, Seoul 120-752.
authors.forename: Dong-In
authors.initials: DI
authors.lastname: Koh
authors.affiliation: the Department of Bioengineering, College of Engineering, Hanyang University, 222 Wangsimni-Ro, Seongdong-Gu, Seoul 133-791, and.
authors.forename: Chae-Ok
authors.initials: CO
authors.lastname: Yun
authors.affiliation: the Department of Bioengineering, College of Engineering, Hanyang University, 222 Wangsimni-Ro, Seongdong-Gu, Seoul 133-791, and.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: the Department of Biological Science, Sungkyunkwan University, 300 Cheon-Cheon Dong, Suwon 440-746, Korea.
authors.forename: Choong-Eun
authors.initials: CE
authors.lastname: Lee
authors.affiliation: the Department of Biological Science, Sungkyunkwan University, 300 Cheon-Cheon Dong, Suwon 440-746, Korea.
authors.forename: Jiyoung
authors.initials: J
authors.lastname: Oh
authors.affiliation: From the Department of Biochemistry and Molecular Biology, Brain Korea 21 Plus Project for Medical Science, Severance Biomedical Research Institute, Yonsei University School of Medicine, 50 Yonsei-Ro, SeoDaeMoon-Gu, Seoul 120-752.
authors.forename: Kunhong
authors.initials: K
authors.lastname: Kim
authors.affiliation: From the Department of Biochemistry and Molecular Biology, Brain Korea 21 Plus Project for Medical Science, Severance Biomedical Research Institute, Yonsei University School of Medicine, 50 Yonsei-Ro, SeoDaeMoon-Gu, Seoul 120-752, mwhur2@yuhs.ac.
authors.forename: Man-Wook
authors.initials: MW
authors.lastname: Hur
mesh_terms: D000107:Acetylation; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D011401:Promoter Regions, Genetic / Q000235:genetics; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D012097:Repressor Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D016329:Sp1 Transcription Factor / Q000378:metabolism; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D006657:Histones; D051741:Kruppel-Like Transcription Factors; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D012097:Repressor Proteins; D016329:Sp1 Transcription Factor; D016159:Tumor Suppressor Protein p53; C092037:ZBTB16 protein, human; D006655:Histone Deacetylases
keywords: Cell Cycle; PLZF; Specificity Protein 1 (Sp1); Transcription Regulation; Transcription Repressor; p21WAF/CDKN1A; p53