G1 tetraploidy checkpoint and the suppression of tumorigenesis

被引:195
作者
Margolis, RL [1 ]
Lohez, OD [1 ]
Andreassen, PR [1 ]
机构
[1] CEA, CNRS, Inst Biol Struct JP Ebel, F-38027 Grenoble 1, France
关键词
aneuploidy; tetraploid checkpoint; p53; pRb; genomic instability;
D O I
10.1002/jcb.10411
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
Checkpoints suppress improper cell cycle progression to ensure that cells maintain the integrity of their genome. During mitosis, a metaphase checkpoint requires the integration of all chromosomes into a metaphase array in the mitotic spindle prior to mitotic exit. Still, mitotic errors occur in mammalian cells with a relatively high frequency. Metaphase represents the last point of control in mitosis. Once the cell commits to anaphase there are no checkpoints to sense segregation defects. In this context, we will explore our recent finding that non-transformed mammalian cells have a checkpoint that acts subsequent to mitotic errors to block the proliferation of cells that have entered G1 with tetraploid status. This arrest is dependent upon both p53 and pRb, and may represent an important function of both p53 and pRb as tumor suppressors. Further, we discuss the possibility that this mechanism may similarly impose G1 arrest in cells that become aneuploid through errors in mitosis.
引用
收藏
页码:673 / 683
页数:11
相关论文
共 78 条
[1]   Mps1 is a kinetochore-associated kinase essential for the vertebrate mitotic checkpoint [J].
Abrieu, A ;
Magnaghi-Jaulin, L ;
Kahana, JA ;
Peter, M ;
Castro, A ;
Vigneron, S ;
Lorca, T ;
Cleveland, DW ;
Labbé, JC .
CELL, 2001, 106 (01) :83-93
[2]   Chromosomal passengers and the (aurora) ABCs of mitosis [J].
Adams, RR ;
Carmena, M ;
Earnshaw, WC .
TRENDS IN CELL BIOLOGY, 2001, 11 (02) :49-54
[3]  
Andreassen PR, 2001, CANCER RES, V61, P7660
[4]   Tetraploid state induces p53-dependent arrest of nontransformed mammalian cells in G1 [J].
Andreassen, PR ;
Lohez, OD ;
Lacroix, FB ;
Margolis, RL .
MOLECULAR BIOLOGY OF THE CELL, 2001, 12 (05) :1315-1328
[5]   Chemical induction of mitotic checkpoint override in mammalian cells results in aneuploidy following a transient tetraploid state [J].
Andreassen, PR ;
Martineau, SN ;
Margolis, RL .
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS, 1996, 372 (02) :181-194
[6]   MICROTUBULE DEPENDENCY OF P34(CDC2) INACTIVATION AND MITOTIC EXIT IN MAMMALIAN-CELLS [J].
ANDREASSEN, PR ;
MARGOLIS, RL .
JOURNAL OF CELL BIOLOGY, 1994, 127 (03) :789-802
[7]   Multiple centrosomes arise from tetraploidy checkpoint failure and mitotic centrosome clusters in p53 and RB pocket protein-compromised cells [J].
Borel, F ;
Lohez, OD ;
Lacroix, FB ;
Margolis, RL .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (15) :9819-9824
[8]   Requirement for p53 and p21 to sustain G2 arrest after DNA damage [J].
Bunz, F ;
Dutriaux, A ;
Lengauer, C ;
Waldman, T ;
Zhou, S ;
Brown, JP ;
Sedivy, JM ;
Kinzler, KW ;
Vogelstein, B .
SCIENCE, 1998, 282 (5393) :1497-1501
[9]  
Bunz F, 2002, CANCER RES, V62, P1129
[10]   Genetic instability and darwinian selection in tumours (Reprinted from Trends in Biochemical Science, vol 12, Dec., 1999) [J].
Cahill, DP ;
Kinzler, KW ;
Vogelstein, B ;
Lengauer, C .
TRENDS IN CELL BIOLOGY, 1999, 9 (12) :M57-M60