title: Transcriptional repression by the Rb-related protein p107.
abstract: The transcription factor DRTF1/E2F is believed to play an important role in regulating cellular proliferation because it undergoes a series of periodic interactions with proteins that are known to be important regulators of the cell cycle, including the retinoblastoma gene product (pRb) and cyclin A. Furthermore, certain viral oncogene products, such as adenovirus E1a, disrupt these DRTF1/E2F complexes by sequestering the associated proteins. p107, a protein that is structurally related to pRb, also binds to DRTF1/E2F, and in this study we investigate the functional consequences of this interaction. We show that p107 can repress E2F binding site-dependent transcription and that the adenovirus E1a protein overcomes p107-mediated transcriptional repression. Two distinct but related proteins, pRb and p107, can therefore repress transcription driven by DRTF1/E2F, whereas the E1a protein overrides the repression. We also demonstrate that the transcription repressing properties of p107 and pRb are influenced by the cell type and by differentiation, because neither protein affects transcription in F9 embryonal carcinoma (EC) cells but both do so efficiently in differentiated derivatives. In this respect, the repressing activities of pRb and p107 inversely correlate with the presence of the cellular E1a-like activity previously documented in F9 EC cells. These data suggest that p107 and pRb exert their biological activities in some but not all cell types.
authors.affiliation: Laboratory of Eukaryotic Molecular Genetics, MRC National Institute for Medical Research, London, United Kingdom.
authors.forename: M
authors.initials: M
authors.lastname: Zamanian
authors.forename: N B
authors.initials: NB
authors.lastname: La Thangue
mesh_terms: D017500:Adenovirus E1A Proteins / Q000494:pharmacology; D002352:Carrier Proteins; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D016213:Cyclins / Q000494:pharmacology*; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D054278:Embryonal Carcinoma Stem Cells; D006801:Humans; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000187:drug effects; D009687:Nuclear Proteins; D011506:Proteins / Q000494:pharmacology*; D016160:Retinoblastoma Protein / Q000494:pharmacology; D056465:Retinoblastoma-Binding Protein 1; D050720:Retinoblastoma-Like Protein p107; D013194:Staining and Labeling; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects*; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D017500:Adenovirus E1A Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D016213:Cyclins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D009687:Nuclear Proteins; D011506:Proteins; C493844:RBL1 protein, human; D016160:Retinoblastoma Protein; D056465:Retinoblastoma-Binding Protein 1; D050720:Retinoblastoma-Like Protein p107; C493735:TFDP1 protein, human; D050680:Transcription Factor DP1; D014157:Transcription Factors