Activation of c-myc uncouples DNA replication from activation of G1-cyclin-dependent kinases

被引:57
作者
Pusch, O
Bernaschek, G
Eilers, M
Hengstschlager, M
机构
[1] UNIV VIENNA,DEPT PRENATAL DIAG & THERAPY,A-1090 VIENNA,AUSTRIA
[2] ZENTRUM MOL BIOL,D-69120 HEIDELBERG,GERMANY
基金
奥地利科学基金会;
关键词
c-Myc; G1-cyclins; cell cycle; initiation of replication;
D O I
10.1038/sj.onc.1201236
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
Proto-oncogenes like c-myc are thought to control exit from the cell cycle rather than progression through the cell cycle itself, We now present a different view of Myc function, Exponentially growing Rat1-MycER(TM) fibroblasts were size-fractionated by centrifugal elutriation, In these cells, activation of cyclin E- and cyclin A- dependent kinases, degradation of p27, hyperphosphorylation of retinoblastoma protein and activation of E2F occur sequentially at specific cell sizes, Upon activation of Myc, however, these transitions all occur simultaneously in small cells immediately after exit from mitosis. In contrast, Myc has no discernible effect on the cell size at which DNA replication is initiated, These data show first that Myc centrals the activity of G1 cyclin-dependent kinases independently from the transition between quiescence and proliferation and from any effect on cell growth in size, These data also provide evidence of at least one dominant mechanism besides activation of E2F and of cyclin E/cdk2 kinase, which prevents DNA replication unless a critical cell size has been reached.
引用
收藏
页码:649 / 656
页数:8
相关论文
共 62 条
  • [1] MYC-MAX-MAD - A TRANSCRIPTION FACTOR NETWORK CONTROLLING CELL-CYCLE PROGRESSION, DIFFERENTIATION AND DEATH
    AMATI, B
    LAND, H
    [J]. CURRENT OPINION IN GENETICS & DEVELOPMENT, 1994, 4 (01) : 102 - 108
  • [2] THE C-MYC PROTEIN INDUCES CELL-CYCLE PROGRESSION AND APOPTOSIS THROUGH DIMERIZATION WITH MAX
    AMATI, B
    LITTLEWOOD, TD
    EVAN, GI
    LAND, H
    [J]. EMBO JOURNAL, 1993, 12 (13) : 5083 - 5087
  • [3] ONCOGENIC ACTIVITY OF THE C-MYC PROTEIN REQUIRES DIMERIZATION WITH MAX
    AMATI, B
    BROOKS, MW
    LEVY, N
    LITTLEWOOD, TD
    EVAN, GI
    LAND, H
    [J]. CELL, 1993, 72 (02) : 233 - 245
  • [4] TRANSCRIPTIONAL ACTIVATION BY THE HUMAN C-MYC ONCOPROTEIN IN YEAST REQUIRES INTERACTION WITH MAX
    AMATI, B
    DALTON, S
    BROOKS, MW
    LITTLEWOOD, TD
    EVAN, GI
    LAND, H
    [J]. NATURE, 1992, 359 (6394) : 423 - 426
  • [5] SEQUENCE-SPECIFIC TRANSCRIPTIONAL ACTIVATION BY MYC AND REPRESSION BY MAX
    AMIN, C
    WAGNER, AJ
    HAY, N
    [J]. MOLECULAR AND CELLULAR BIOLOGY, 1993, 13 (01) : 383 - 390
  • [6] ADENOVIRUS E1A PROTEINS CAN DISSOCIATE HETEROMERIC COMPLEXES INVOLVING THE E2F TRANSCRIPTION FACTOR - A NOVEL MECHANISM FOR E1A TRANSACTIVATION
    BAGCHI, S
    RAYCHAUDHURI, P
    NEVINS, JR
    [J]. CELL, 1990, 62 (04) : 659 - 669
  • [7] THE ORNITHINE DECARBOXYLASE GENE IS A TRANSCRIPTIONAL TARGET OF C-MYC
    BELLOFERNANDEZ, C
    PACKHAM, G
    CLEVELAND, JL
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (16) : 7804 - 7808
  • [8] TRANSCRIPTIONAL REGULATION - FLIPPING THE MYC SWITCH
    BERNARDS, R
    [J]. CURRENT BIOLOGY, 1995, 5 (08) : 859 - 861
  • [9] SEQUENCE-SPECIFIC DNA-BINDING BY THE C-MYC PROTEIN
    BLACKWELL, TK
    KRETZNER, L
    BLACKWOOD, EM
    EISENMAN, RN
    WEINTRAUB, H
    [J]. SCIENCE, 1990, 250 (4984) : 1149 - 1151
  • [10] MAX - A HELIX-LOOP-HELIX ZIPPER PROTEIN THAT FORMS A SEQUENCE-SPECIFIC DNA-BINDING COMPLEX WITH MYC
    BLACKWOOD, EM
    EISENMAN, RN
    [J]. SCIENCE, 1991, 251 (4998) : 1211 - 1217