title: Proto-oncogene FBI-1 (Pokemon/ZBTB7A) represses transcription of the tumor suppressor Rb gene via binding competition with Sp1 and recruitment of co-repressors.
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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Brain Korea 21 Project for Medical Sciences, Yonsei University School of Medicine, 134, ShinChon-Dong, Seoul 120-752, Korea.
authors.forename: Bu-Nam
authors.initials: BN
authors.lastname: Jeon
authors.forename: Jung-Yoon
authors.initials: JY
authors.lastname: Yoo
authors.forename: Won-Il
authors.initials: WI
authors.lastname: Choi
authors.forename: Choong-Eun
authors.initials: CE
authors.lastname: Lee
authors.forename: Ho-Geun
authors.initials: HG
authors.lastname: Yoon
authors.forename: Man-Wook
authors.initials: MW
authors.lastname: Hur
mesh_terms: D020727:ADP-Ribosylation Factors / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D002453:Cell Cycle / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster; D006367:HeLa Cells; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D032446:Myoblasts / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D020218:Response Elements / Q000502:physiology*; D016160:Retinoblastoma Protein / Q000378:metabolism*; D016329:Sp1 Transcription Factor / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology*
chemical_list: D004268:DNA-Binding Proteins; D006657:Histones; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D016160:Retinoblastoma Protein; D016329:Sp1 Transcription Factor; D014157:Transcription Factors; C485514:ZBTB7A protein, human; D006655:Histone Deacetylases; D020727:ADP-Ribosylation Factors
references.citation: Gene. 1999 Oct 1;238(2):291-300
references.pmid: 10570957
references.citation: Oncogene. 2006 Aug 28;25(38):5302-8
references.pmid: 16936751
references.citation: J Biol Chem. 2002 Jul 26;277(30):26761-8
references.pmid: 12004059
references.citation: Mol Cell Biol. 2003 Apr;23(8):2893-906
references.pmid: 12665587
references.citation: J Biol Chem. 2003 Aug 1;278(31):29327-35
references.pmid: 12750370
references.citation: Nucleic Acids Res. 2004;32(2):590-7
references.pmid: 14752047
references.citation: J Biol Chem. 2004 Mar 19;279(12):11711-8
references.pmid: 14701838
references.citation: Nature. 1986 Oct 16-22;323(6089):643-6
references.pmid: 2877398
references.citation: Science. 1987 Mar 13;235(4794):1394-9
references.pmid: 3823889
references.citation: Cell. 1987 Dec 24;51(6):1079-90
references.pmid: 3319186
references.citation: Science. 1988 Dec 16;242(4885):1563-6
references.pmid: 3201247
references.citation: Nature. 1991 Sep 5;353(6339):83-6
references.pmid: 1881452
references.citation: Cell. 1991 Oct 18;67(2):293-302
references.pmid: 1655277
references.citation: Science. 1992 Oct 16;258(5081):424-9
references.pmid: 1411535
references.citation: Cell Growth Differ. 1994 May;5(5):467-74
references.pmid: 8049153
references.citation: Cancer Res. 1997 Aug 1;57(15):3145-8
references.pmid: 9242441
references.citation: J Biol Chem. 1999 Jan 1;274(1):20-8
references.pmid: 9867805
references.citation: Oncogene. 1999 Jan 14;18(2):365-75
references.pmid: 9927193
references.citation: Nucleic Acids Res. 1999 Mar 1;27(5):1251-62
references.pmid: 9973611
references.citation: Blood. 1999 Sep 15;94(6):1987-97
references.pmid: 10477728
references.citation: J Biol Chem. 2004 Nov 5;279(45):47081-91
references.pmid: 15337766
references.citation: Biochem Biophys Res Commun. 2004 Dec 17;325(3):653-9
references.pmid: 15541338
references.citation: Nature. 2005 Jan 20;433(7023):278-85
references.pmid: 15662416
references.citation: Genes Cells. 2005 Jul;10(7):717-31
references.pmid: 15966902
references.citation: J Biol Chem. 2005 Jul 29;280(30):28061-71
references.pmid: 15878880
references.citation: J Biol Chem. 2005 Jul 29;280(30):27783-91
references.pmid: 15917220
references.citation: Cancer Res. 2005 Oct 1;65(19):8575-8
references.pmid: 16204018
references.citation: Oncogene. 2006 Aug 28;25(38):5210-9
references.pmid: 16936739
references.citation: Mol Biol Cell. 2002 Mar;13(3):915-29
references.pmid: 11907272