title: pRB and p107/p130 are required for the regulated expression of different sets of E2F responsive genes.
abstract: The activity of the E2F transcription factor is controlled by physical association with the retinoblastoma protein (pRB) and two related proteins, p107 and p130. The pRB family members are thought to control different aspects of E2F activity, but it has been unclear what the respective functions of these proteins might be. To dissect the specific functions of pRB, p107, and p130 we have investigated how the expression of E2F-regulated genes is changed in cultures of primary cells lacking each of these family members. Whereas no changes were found in the expression of E2F-target genes in cells lacking either p107 or p130, deregulated expression of E2F targets was seen in cells lacking pRB and in cells lacking both p107 and p130. Surprisingly, the genes that were disregulated in these two settings were completely different. These findings show that pRB and p107/p130 indeed provide different functions in E2F regulation and identify target genes that are dependent on pRB family proteins for their normal expression.
authors.affiliation: Massachusetts General Hospital Cancer Center, Charlestown 02129, USA.
authors.forename: R K
authors.initials: RK
authors.lastname: Hurford
authors.forename: D
authors.initials: D
authors.lastname: Cobrinik
authors.forename: M H
authors.initials: MH
authors.lastname: Lee
authors.forename: N
authors.initials: N
authors.lastname: Dyson
mesh_terms: D000818:Animals; D002352:Carrier Proteins; D002453:Cell Cycle / Q000235:genetics; D018797:Cell Cycle Proteins; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D004622:Embryo, Mammalian / Q000166:cytology; D005347:Fibroblasts / Q000166:cytology; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D051379:Mice; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011506:Proteins; D016160:Retinoblastoma Protein / Q000172:deficiency / Q000378:metabolism*; D056465:Retinoblastoma-Binding Protein 1; D050720:Retinoblastoma-Like Protein p107; D050717:Retinoblastoma-Like Protein p130; D015534:Trans-Activators; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection
chemical_list: C533431:Arid4a protein, mouse; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D016895:Culture Media, Serum-Free; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; C499306:Mybl2 protein, mouse; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011506:Proteins; C489485:Rbl1 protein, mouse; C493838:Rbl2 protein, mouse; D016160:Retinoblastoma Protein; D056465:Retinoblastoma-Binding Protein 1; D050720:Retinoblastoma-Like Protein p107; D050717:Retinoblastoma-Like Protein p130; D015534:Trans-Activators; D050680:Transcription Factor DP1; D014157:Transcription Factors