DEREGULATION OF SPECIFIC E2F COMPLEXES BY THE V-MOS ONCOGENE

The product of the c-mos proto-oncogene is a protein kinase that is no rmally expressed in germ cells and functions during oocyte maturation, It has been shown, however, that inappropriate expression of either t he viral or cellular mos gene can induce neoplastic progression in som atic cells. Furthermore, v-mos-transformed NIH3T3 cells will undergo a rrest of proliferation in early G1 upon serum withdrawal but are unabl e to appropriately downregulate cell cycle regulatory proteins, such a s cyclin and cdc2 proteins, that normally are down-regulated in quiesc ent, untransformed NIH3T3 cells. Since the levels of these proteins ar e partially transcriptionally controlled, me investigated whether ther e were alterations in the expression of E2F and AP-1 transcription fac tor complexes. Indeed, the putative G0/G1-specific p130-E2F complex th at is normally observed during low serum-induced cell cycle arrest in NIH3T3 cells is not present in serum starved v-mos-transformed cells. instead, G1-phase arrested v-mos-transformed cells stably express two E2F protein complexes that are normally observed only during S-phase i n untransformed cells, The elevation of these complexes in arrested v- mos-transformed cells may be the cause of the transcriptional activati on of the E2F-regulated genes cdc2, DHFR, Cyclin A, and E2F1 seen in s erum starved v-mos-transformed cells. In addition, there are high leve ls of AP-1 DNA binding activity in serum starved v-mos-transformed cel ls compared to very low amounts in nontransformed cells. This altered regulation of transcription factor complexes and cell cycle control pr oteins upon serum withdrawal may provide a mechanism for the uncontrol led cell growth associated with neoplastic transformation induced by c ertain proto-oncogenes.