Mice thrive without Cdk4 and Cdk2

被引:89
作者
Barriere, Cedric [1 ,2 ]
Santamaria, David [1 ]
Cerqueira, Antonio [1 ]
Galan, Javier [1 ]
Martin, Alberto [1 ]
Ortega, Sagrario [1 ]
Malumbres, Marcos [1 ]
Dubus, Pierre [2 ]
Barbacid, Mariano [1 ]
机构
[1] CNIO, Biotechnol Program, E-28029 Madrid, Spain
[2] Univ Bordeaux 2, EA2406, F-33076 Bordeaux, France
来源
MOLECULAR ONCOLOGY | 2007年 / 1卷 / 01期
关键词
Cyclin-dependent kinases; Mouse development; Cell proliferation; Conditional knock outs; Liver regeneration;
D O I
10.1016/j.molonc.2007.03.001
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Mammalian cell division is thought to be driven by sequential activation of several Cyclin-dependent kinases (Cdk), mainly Cdk4, Cdk6, Cdk2 and Cdk1. Since mice lacking Cdk4, Cdk6 or Cdk2 are viable, it has been proposed that they play compensatory roles. We report here that mice lacking Cdk4 and Cdk2 complete embryonic development to die shortly thereafter presumably due to heart failure. However, conditional ablation of Cdk2 in adult mice lacking Cdk4 does not result in obvious abnormalities. Moreover, these double mutant mice recover normally after partial hepatectomy. In culture, Cdk4(-/-); Cdk2(-/-) embryonic fibroblasts become immortal, display robust pRb phosphorylation. and have normal S phase kinetics. These observations indicate that Cdk4 and Cdk2 are dispensable for the mammalian cell cycle and for adult homeostasis. (C) 2007 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:72 / 83
页数:12
相关论文
共 21 条
  • [1] Regulation of the retinoblastoma tumor suppressor protein by cyclin/cdks
    Adams, PD
    [J]. BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER, 2001, 1471 (03): : M123 - M133
  • [2] Cdc2-cyclin E complexes regulate the G1/S phase transition
    Aleem, E
    Kiyokawa, H
    Kaldis, P
    [J]. NATURE CELL BIOLOGY, 2005, 7 (08) : 831 - U93
  • [3] Cdk2 knockout mice are viable
    Berthet, C
    Aleem, E
    Coppola, V
    Tessarollo, L
    Kaldis, P
    [J]. CURRENT BIOLOGY, 2003, 13 (20) : 1775 - 1785
  • [4] Combined loss of Cdk2 and Cdk4 results in embryonic lethality and Rb hypophosphorylation
    Berthet, Cyril
    Klarmann, Kimberly D.
    Hilton, Mary Beth
    Suh, Hyung Chan
    Keller, Jonathan R.
    Kiyokawa, Hiroaki
    Kaldis, Philipp
    [J]. DEVELOPMENTAL CELL, 2006, 10 (05) : 563 - 573
  • [5] The regulation of E2F by pRB-family proteins
    Dyson, N
    [J]. GENES & DEVELOPMENT, 1998, 12 (15) : 2245 - 2262
  • [6] Ligand-activated site-specific recombination in mice
    Feil, R
    Brocard, J
    Mascrez, B
    LeMeur, M
    Metzger, D
    Chambon, P
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (20) : 10887 - 10890
  • [7] Tumor induction by an endogenous K-ras oncogene is highly dependent on cellular context
    Guerra, C
    Mijimolle, N
    Dhawahir, A
    Dubus, P
    Barradas, M
    Serrano, M
    Campuzano, V
    Barbacid, M
    [J]. CANCER CELL, 2003, 4 (02) : 111 - 120
  • [8] Mouse development and cell proliferation in the absence of D-cyclins
    Kozar, K
    Ciemerych, MA
    Rebel, VI
    Shigematsu, H
    Zagozdon, A
    Sicinska, E
    Geng, Y
    Yu, QY
    Bhattacharya, S
    Bronson, RT
    Akashi, K
    Sicinski, P
    [J]. CELL, 2004, 118 (04) : 477 - 491
  • [9] Mammalian cells cycle without the D-type cyclin-elependent kinases Cdk4 and Cdk6
    Malumbres, M
    Sotillo, R
    Santamaria, D
    Galán, J
    Cerezo, A
    Ortega, S
    Dubus, P
    Barbacid, M
    [J]. CELL, 2004, 118 (04) : 493 - 504
  • [10] Mammalian cyclin-dependent kinases
    Malumbres, M
    Barbacid, M
    [J]. TRENDS IN BIOCHEMICAL SCIENCES, 2005, 30 (11) : 630 - 641