Deregulation of specific E2F complexes by the v-mos oncogene

被引:8
作者
Afshari, CA
Rhodes, N
Paules, RS
Mudryj, M
机构
[1] DUKE UNIV,MED CTR,DEPT MED,DURHAM,NC 27705
[2] DURHAM VA VET ADM MED CTR,GRECC 182,DURHAM,NC 27705
[3] CTR STUDY AGING & HUMAN DEV,DURHAM,NC 27705
[4] NIEHS,GROWTH CONTROL & CANC GRP,RES TRIANGLE PK,NC 27709
[5] UNIV CALIF DAVIS,SCH MED,DEPT MED MICROBIOL & IMMUNOL,DAVIS,CA 95616
[6] MARTINEZ VET ADM,MARTINEZ,CA
关键词
E2F; mos oncogene; cell cycle;
D O I
10.1038/sj.onc.1201157
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The product of the c-mos proto-oncogene is a protein kinase that is normally expressed in germ cells and functions during oocyte maturation, It has been shown, however, that inappropriate expression of either the viral or cellular mos gene can induce neoplastic progression in somatic cells. Furthermore, v-mos-transformed NIH3T3 cells will undergo arrest of proliferation in early G1 upon serum withdrawal but are unable to appropriately downregulate cell cycle regulatory proteins, such as cyclin and cdc2 proteins, that normally are down-regulated in quiescent, untransformed NIH3T3 cells. Since the levels of these proteins are partially transcriptionally controlled, me investigated whether there were alterations in the expression of E2F and AP-1 transcription factor complexes. Indeed, the putative G0/G1-specific p130-E2F complex that 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 in untransformed cells, The elevation of these complexes in arrested v-mos-transformed cells may be the cause of the transcriptional activation of the E2F-regulated genes cdc2, DHFR, Cyclin A, and E2F1 seen in serum starved v-mos-transformed cells. In addition, there are high levels of AP-1 DNA binding activity in serum starved v-mos-transformed cells compared to very low amounts in nontransformed cells. This altered regulation of transcription factor complexes and cell cycle control proteins upon serum withdrawal may provide a mechanism for the uncontrolled cell growth associated with neoplastic transformation induced by certain proto-oncogenes.
引用
收藏
页码:3029 / 3038
页数:10
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