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Proto-oncogene FBI-1 (Pokemon/ZBTB7A) represses transcription of the tumor suppressor Rb gene via binding competition with Sp1 and recruitment of co-repressors

Authors
 Bu-Nam Jeon  ;  Jung-Yoon Yoo  ;  Won-Il Choi  ;  Choong-Eun Lee  ;  Ho-Geun Yoon  ;  Man-Wook Hur 
Citation
 JOURNAL OF BIOLOGICAL CHEMISTRY, Vol.283(48) : 33199-33210, 2008 
Journal Title
 JOURNAL OF BIOLOGICAL CHEMISTRY 
ISSN
 0021-9258 
Issue Date
2008
MeSH
ADP-Ribosylation Factors/antagonists & inhibitors ; ADP-Ribosylation Factors/metabolism ; Animals ; Cell Cycle/physiology ; Cell Differentiation/physiology ; DNA-Binding Proteins/metabolism* ; Drosophila melanogaster ; HeLa Cells ; Histone Deacetylases/metabolism ; Histones/metabolism ; Humans ; Myoblasts/metabolism ; Protein Binding/physiology ; Protein Structure, Tertiary/physiology ; Proto-Oncogene Proteins/metabolism* ; Response Elements/physiology* ; Retinoblastoma Protein/metabolism* ; Sp1 Transcription Factor/metabolism* ; Transcription Factors/metabolism* ; Transcription, Genetic/physiology*
Keywords
ADP-Ribosylation Factors/antagonists & inhibitors ; ADP-Ribosylation Factors/metabolism ; Animals ; Cell Cycle/physiology ; Cell Differentiation/physiology ; DNA-Binding Proteins/metabolism* ; Drosophila melanogaster ; HeLa Cells ; Histone Deacetylases/metabolism ; Histones/metabolism ; Humans ; Myoblasts/metabolism ; Protein Binding/physiology ; Protein Structure, Tertiary/physiology ; Proto-Oncogene Proteins/metabolism* ; Response Elements/physiology* ; Retinoblastoma Protein/metabolism* ; Sp1 Transcription Factor/metabolism* ; Transcription Factors/metabolism* ; Transcription, Genetic/physiology*
Abstract
FBI-1 (also called Pokemon/ZBTB7A) is a BTB/POZ-domain Krüppel-like zinc-finger transcription factor. Recently, FBI-1 was characterized as a proto-oncogenic protein, which represses tumor suppressor ARF gene transcription. The expression of FBI-1 is increased in many cancer tissues. We found that FBI-1 potently represses transcription of the Rb gene, a tumor suppressor gene important in cell cycle arrest. FBI-1 binds to four GC-rich promoter elements (FREs) located at bp -308 to -188 of the Rb promoter region. The Rb promoter also contains two Sp1 binding sites: GC-box 1 (bp -65 to -56) and GC-box 2 (bp -18 to -9), the latter of which is also bound by FBI-1. We found that FRE3 (bp -244 to -236) is also a Sp1 binding element. FBI-1 represses transcription of the Rb gene not only by binding to the FREs, but also by competing with Sp1 at the GC-box 2 and the FRE3. By binding to the FREs and/or the GC-box, FBI-1 represses transcription of the Rb gene through its POZ-domain, which recruits a co-repressor-histone deacetylase complex and deacetylates histones H3 and H4 at the Rb gene promoter. FBI-1 inhibits C2C12 myoblast cell differentiation by repressing Rb gene expression
Files in This Item:
T200800690.pdf Download
DOI
10.1074/jbc.M802935200
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
Yonsei Authors
Yoo, Jung Yoon(유정윤) ORCID logo https://orcid.org/0000-0001-9366-3863
Yoon, Ho Geun(윤호근) ORCID logo https://orcid.org/0000-0003-2718-3372
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/22282913/106940
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