CHK2 kinase: cancer susceptibility and cancer therapy - two sides of the same coin?

被引:238
作者
Antoni, Laurent
Sodha, Nayanta
Collins, Ian
Garrett, Michelle D.
机构
[1] Canc Res UK Ctr Canc Therapeut, Inst Canc Res, Haddow Labs, Sutton SM2 5NG, Surrey, England
[2] Royal Marsden NHS Fdn Trust, Surrey SM2 5PT, England
关键词
D O I
10.1038/nrc2251
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
In the past decade, CHK2 has emerged as an important multifunctional player in the DNA-damage response signalling pathway. Parallel studies of the human CHEK2 gene have also highlighted its role as a candidate multiorgan tumour susceptibility gene rather than a highly penetrant predisposition gene for Li-Fraumeni syndrome. As discussed here, our current understanding of CHK2 function in tumour cells, in both a biological and genetic context, suggests that targeted modulation of the active kinase or exploitation of its loss in tumours could prove to be effective anti-cancer strategies.
引用
收藏
页码:925 / 936
页数:12
相关论文
共 145 条
[1]   Checkpoint kinase 2 (Chk2) monomers or dimers phosphorylate Cdc25C after DNA damage regardless of threonine 68 phosphorylation [J].
Ahn, J ;
Prives, C .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (50) :48418-48426
[2]   Questioning the role of checkpoint kinase 2 in the p53 DNA damage response [J].
Ahn, JW ;
Urist, M ;
Prives, C .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (23) :20480-20489
[3]   Phosphorylation of threonine 68 promotes oligomerization and autophosphorylation of the Chk2 protein kinase via the forkhead-associated domain [J].
Ahn, JY ;
Li, XH ;
Davis, HL ;
Canman, CE .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (22) :19389-19395
[4]  
Ahn JY, 2000, CANCER RES, V60, P5934
[5]   Analysis of CHK2 in patients with myelodysplastic syndromes [J].
Aktas, D ;
Arno, MJ ;
Rassool, F ;
Mufti, GJ .
LEUKEMIA RESEARCH, 2002, 26 (11) :985-987
[6]  
ALIOUATDENIS CM, 2005, MOL CANCER RES, V3, P7
[7]   THE SAD1/RAD53 PROTEIN-KINASE CONTROLS MULTIPLE CHECKPOINTS AND DNA DAMAGE-INDUCED TRANSCRIPTION IN YEAST [J].
ALLEN, JB ;
ZHOU, Z ;
SIEDE, W ;
FRIEDBERG, EC ;
ELLEDGE, SJ .
GENES & DEVELOPMENT, 1994, 8 (20) :2401-2415
[8]   Checkpoint kinase inhibitors: SAR and radioprotective properties of a series of 2-arylbenzimidazoles [J].
Arienti, KL ;
Brunmark, A ;
Axe, FU ;
McClure, K ;
Lee, A ;
Blevitt, J ;
Neff, DK ;
Huang, LM ;
Crawford, S ;
Pandit, CR ;
Karlsson, L ;
Breitenbucher, JG .
JOURNAL OF MEDICINAL CHEMISTRY, 2005, 48 (06) :1873-1885
[9]   Priming phosphorylation of Chk2 by polo-like kinase 3 (Plk3) mediates its full activation by ATM and a downstream checkpoint in response to DNA damage [J].
Bahassi, EM ;
Myer, DL ;
McKenney, RJ ;
Hennigan, RF ;
Stambrook, PJ .
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS, 2006, 596 (1-2) :166-176
[10]   Mammalian Polo-like kinase 3 (PIU) is a multifunctional protein involved in stress response pathways [J].
Bahassi, EM ;
Conn, CW ;
Myer, DL ;
Hennigan, RF ;
McGowan, CH ;
Sanchez, Y ;
Stambrook, PJ .
ONCOGENE, 2002, 21 (43) :6633-6640