Cooperating oncogenes converge to regulate cyclin/cdk complexes

被引:201
作者
Lloyd, AC
Obermuller, F
Staddon, S
Barth, CF
McMahon, M
Land, H
机构
[1] IMPERIAL CANC RES FUND,LONDON WC2A 3PX,ENGLAND
[2] DNAX RES INST MOL & CELLULAR BIOL INC,PALO ALTO,CA 94304
关键词
cell cycle; oncogenes; cyclin-dependent kinase; p21(Cip1); Raf; p53;
D O I
10.1101/gad.11.5.663
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The cooperation of oncogenes in the transformation of primary rat Schwann cells is a strikingly synergistic process. We have explored the molecular mechanisms involved. Activation of an inducible Raf kinase results in morphologically transformed cells that are arrested in G(1), via the induction of p21(Cip1) and subsequent inhibition of cyclin/cdk activity. In contrast, coexpression of SV40 large T (LT) or a dominant-negative mutant of p53 abolishes p21(Cip1) induction and alleviates the growth arrest. Moreover in this scenario, Raf activation results in an increase in the specific activity of cyclin/cdk complexes with Raf and LT cooperating to superinduce cyclin A/cdk2 activity and stimulate proliferation in the absence of mitogens. Thus, signaling by Raf and its cooperating partners converges at the regulation of cyclin/cdk complexes, with the cellular responses to Raf modulated by p53.
引用
收藏
页码:663 / 677
页数:15
相关论文
共 73 条
  • [1] THE NF1 LOCUS ENCODES A PROTEIN FUNCTIONALLY RELATED TO MAMMALIAN GAP AND YEAST IRA PROTEINS
    BALLESTER, R
    MARCHUK, D
    BOGUSKI, M
    SAULINO, A
    LETCHER, R
    WIGLER, M
    COLLINS, F
    [J]. CELL, 1990, 63 (04) : 851 - 859
  • [2] ABERRANT REGULATION OF RAS PROTEINS IN MALIGNANT-TUMOR CELLS FROM TYPE-1 NEUROFIBROMATOSIS PATIENTS
    BASU, TN
    GUTMANN, DH
    FLETCHER, JA
    GLOVER, TW
    COLLINS, FS
    DOWNWARD, J
    [J]. NATURE, 1992, 356 (6371) : 713 - 715
  • [3] BATES S, 1994, ONCOGENE, V9, P1633
  • [4] STUDIES ON CULTURED RAT SCHWANN-CELLS .1. ESTABLISHMENT OF PURIFIED POPULATIONS FROM CULTURES OF PERIPHERAL-NERVE
    BROCKES, JP
    FIELDS, KL
    RAFF, MC
    [J]. BRAIN RESEARCH, 1979, 165 (01) : 105 - 118
  • [5] RADIATION-INDUCED CELL-CYCLE ARREST COMPROMISED BY P21 DEFICIENCY
    BRUGAROLAS, J
    CHANDRASEKARAN, C
    GORDON, JI
    BEACH, D
    JACKS, T
    HANNON, GJ
    [J]. NATURE, 1995, 377 (6549) : 552 - 557
  • [6] ABNORMAL REGULATION OF MAMMALIAN P21(RAS) CONTRIBUTES TO MALIGNANT-TUMOR GROWTH IN VONRECKLINGHAUSEN (TYPE-1) NEUROFIBROMATOSIS
    DECLUE, JE
    PAPAGEORGE, AG
    FLETCHER, JA
    DIEHL, SR
    RATNER, N
    VASS, WC
    LOWY, DR
    [J]. CELL, 1992, 69 (02) : 265 - 273
  • [7] MICE LACKING P21(C/P1/WAF1) UNDERGO NORMAL DEVELOPMENT, BUT ARE DEFECTIVE IN G1 CHECKPOINT CONTROL
    DENG, CX
    ZHANG, PM
    HARPER, JW
    ELLEDGE, SJ
    LEDER, P
    [J]. CELL, 1995, 82 (04) : 675 - 684
  • [8] P53-DEPENDENT INHIBITION OF CYCLIN-DEPENDENT KINASE-ACTIVITIES IN HUMAN FIBROBLASTS DURING RADIATION-INDUCED G1 ARREST
    DULIC, V
    KAUFMANN, WK
    WILSON, SJ
    TLSTY, TD
    LEES, E
    HARPER, JW
    ELLEDGE, SJ
    REED, SI
    [J]. CELL, 1994, 76 (06) : 1013 - 1023
  • [9] WAF1, A POTENTIAL MEDIATOR OF P53 TUMOR SUPPRESSION
    ELDEIRY, WS
    TOKINO, T
    VELCULESCU, VE
    LEVY, DB
    PARSONS, R
    TRENT, JM
    LIN, D
    MERCER, WE
    KINZLER, KW
    VOGELSTEIN, B
    [J]. CELL, 1993, 75 (04) : 817 - 825
  • [10] Dependence of cyclin E-CDK2 kinase activity on cell anchorage
    Fang, F
    Orend, G
    Watanabe, N
    Hunter, T
    Ruoslahti, E
    [J]. SCIENCE, 1996, 271 (5248) : 499 - 502