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
    Ahn, J
    Prives, C
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (50) : 48418 - 48426
  • [2] Questioning the role of checkpoint kinase 2 in the p53 DNA damage response
    Ahn, JW
    Urist, M
    Prives, C
    [J]. 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
    Ahn, JY
    Li, XH
    Davis, HL
    Canman, CE
    [J]. 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
    Aktas, D
    Arno, MJ
    Rassool, F
    Mufti, GJ
    [J]. 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
    ALLEN, JB
    ZHOU, Z
    SIEDE, W
    FRIEDBERG, EC
    ELLEDGE, SJ
    [J]. GENES & DEVELOPMENT, 1994, 8 (20) : 2401 - 2415
  • [8] Checkpoint kinase inhibitors: SAR and radioprotective properties of a series of 2-arylbenzimidazoles
    Arienti, KL
    Brunmark, A
    Axe, FU
    McClure, K
    Lee, A
    Blevitt, J
    Neff, DK
    Huang, LM
    Crawford, S
    Pandit, CR
    Karlsson, L
    Breitenbucher, JG
    [J]. 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
    Bahassi, EM
    Myer, DL
    McKenney, RJ
    Hennigan, RF
    Stambrook, PJ
    [J]. 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
    Bahassi, EM
    Conn, CW
    Myer, DL
    Hennigan, RF
    McGowan, CH
    Sanchez, Y
    Stambrook, PJ
    [J]. ONCOGENE, 2002, 21 (43) : 6633 - 6640