TRANSCRIPTIONAL REPRESSION BY THE RB-RELATED PROTEIN-P107

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.