Cyclin-dependent kinase 2 is essential for meiosis but not for mitotic cell division in mice

被引：680
作者：
Ortega, S
Prieto, I
Odajima, J
Martín, A
Dubus, P
Sotillo, R
Barbero, JL
Malumbres, M
Barbacid, M
机构：
[1] Ctr Nacl Invest Oncol, Mol Oncol Program, E-28029 Madrid, Spain
[2] CSIC, Ctr Nacl Biotecnol, Dept Immunol & Oncol, E-28029 Madrid, Spain
[3] Univ Bordeaux 2, EA 2406, F-33076 Bordeaux, France
来源：
NATURE GENETICS | 2003年 / 35卷 / 01期
关键词：
D O I：
10.1038/ng1232
中图分类号：
Q3 [遗传学];
学科分类号：
071007 ; 090102 ;
摘要：
We targeted the locus encoding the cyclin-dependent kinase 2 (CDK2) by homologous recombination in mouse embryonic stem (ES) cells. Embryonic fibroblasts lacking CDK2 proliferate normally and become immortal after continuous passage in culture. Elimination of a conditional Cdk2 allele in immortal cells does not have a significant effect on proliferation. Cdk2(-/-) mice are viable and survive for up to two years, indicating that CDK2 is also dispensable for proliferation and survival of most cell types. But CDK2 is essential for completion of prophase I during meiotic cell division in male and female germ cells, an unforeseen role for this cell cycle kinase.
引用
收藏
页码：25 / 31
页数：7
相关论文
共 52 条
[1]  
Ashley T, 2001, J CELL SCI, V114, P685
[2]   Mouse MutS-like protein Msh5 is required for proper chromosome synapsis in male and female meiosis [J].
de Vries, SS ;
Baart, EB ;
Dekker, M ;
Siezen, A ;
de Rooij, DG ;
de Boer, P ;
te Riele, H .
GENES & DEVELOPMENT, 1999, 13 (05) :523-531
[3]   Meiotic prophase abnormalities and metaphase cell death in MLH1-deficient mouse spermatocytes: Insights into regulation of spermatogenic progress [J].
Eaker, S ;
Cobb, J ;
Pyle, A ;
Handel, MA .
DEVELOPMENTAL BIOLOGY, 2002, 249 (01) :85-95
[4]   A NEW HUMAN P34 PROTEIN-KINASE, CDK2, IDENTIFIED BY COMPLEMENTATION OF A CDC28 MUTATION IN SACCHAROMYCES-CEREVISIAE, IS A HOMOLOG OF XENOPUS-EG1 [J].
ELLEDGE, SJ ;
SPOTTSWOOD, MR .
EMBO JOURNAL, 1991, 10 (09) :2653-2659
[5]   The mouse Mps1p-like kinase regulates centrosome duplication [J].
Fisk, HA ;
Winey, M .
CELL, 2001, 106 (01) :95-104
[6]   Cyclin E uses Cdc6 as a chromatin-associated receptor required for DNA replication [J].
Furstenthal, L ;
Kaiser, BK ;
Swanson, C ;
Jackson, PK .
JOURNAL OF CELL BIOLOGY, 2001, 152 (06) :1267-1278
[7]   The oncogenic activity of cyclin E is not confined to Cdk2 activation alone but relies on several other, distinct functions of the protein [J].
Geisen, C ;
Möröy, T .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (42) :39909-39918
[8]  
GENG Y, IN PRESS CELL
[9]   Cdk2 kinase is required for entry into mitosis as a positive regulator of Cdc2-cyclin B kinase activity [J].
Guadagno, TM ;
Newport, JW .
CELL, 1996, 84 (01) :73-82
[10]  
Hanks MC, 1998, DEVELOPMENT, V125, P4521
123456