期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 283, 期 48, 页码 33199-33210出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M802935200
关键词
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资金
- National Research Laboratory [ROA-2003000-10318-0]
- Korea Science and Engineering Foundation of the Korea Ministry of Science and Technology [R13-2002054-05002-0]
FBI-1 (also called Pokemon/ZBTB7A) is a BTB/POZ-domain Kruppel-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.
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