CELL CYCLE-SPECIFIC ASSOCIATION OF E2F WITH THE P130 E1A-BINDING PROTEIN

Association of the E2F transcription factor with the pRb and p107 prot eins appears to regulate the activity of E2F and, in turn, affect cell cycle progression. We found, however, that pRb and p107 are only mino r E2F-associated proteins in G0/G1 mouse fibroblasts, and we sought to identify the major E2F partner protein in these cells. Because the ad enovirus E1A oncoprotein seemed able to bind to the G0 E2F partner, we enriched for proteins that associated both with an E2F-binding site D NA column and with E1A. The major species in G0 and early G1 fibroblas ts detected with this approach had properties identical to the pRb- an d p107-related p130 protein. In serum-stimulated cells, p107 replaced p130 as the major E2F-associated protein near the G1/S border, concomi tant with an increase in p107 protein levels. p130-E2F complexes resem bled p107-E2F complexes in their ability to bind to cyclin-cdk kinases , and they appeared to be associated with the cyclin E-cdk2 kinase in late G1 cells. These observations indicate that E2F transcription fact ors are regulated by a succession of partner proteins with which they associate during defined stages of the cell cycle.