INHIBITION OF CELL-PROLIFERATION BY P107, A RELATIVE OF THE RETINOBLASTOMA PROTEIN

The cellular protein p107 shares many structural and biochemical featu res with the retinoblastoma gene product, pRB. We have isolated a full -length cDNA for human p107 and have used this clone to study the func tion of p107. We show that, like pRB, p107 is a potent inhibitor of E2 F-mediated trans-activation, and overexpression of p107 can inhibit pr oliferation in certain cell types, arresting sensitive cells in G1. Se veral experiments, however, showed that growth inhibition by pRB and p 107 did not occur through the same mechanism. First, in the cervical c arcinoma cell line C33A, p107 was able to block cell proliferation, wh ereas pRB could not, even though both proteins were potent inhibitors of E2F-mediated transcription in this cell line. Second, growth arrest by pRB and p107 was rescued differentially by various cell cycle regu lators. Third, some mutants of p107 that cannot associate with adenovi rus E1A were still able to inhibit cell proliferation, whereas analogo us mutants in pRB are known to be unable to block cell growth. Togethe r, these results suggest a biological role of p107 that is related, bu t not identical, to that of pRB.