MKK7 and ARF New players in the DNA damage response scenery

被引:12
作者
Kotsinas, Athanassios [1 ]
Papanagnou, Panagiota [1 ]
Galanos, Panagiotis [1 ]
Schramek, Daniel [2 ]
Townsend, Paul [3 ,4 ]
Penninger, Josef M. [5 ]
Bartek, Jiri [6 ,7 ]
Gorgoulis, Vassilis G. [1 ,3 ,4 ,8 ]
机构
[1] Univ Athens, Sch Med, Dept Histol & Embryol, Mol Carcinogenesis Grp, GR-11527 Athens, Greece
[2] Rockefeller Univ, Howard Hughes Med Inst, Lab Mammalian Cell Biol & Dev, New York, NY 10021 USA
[3] Univ Manchester, Manchester Acad Hlth Sci Ctr, Fac Inst Canc Sci, Manchester, Lancs, England
[4] Univ Manchester, Manchester Acad Hlth Sci Ctr, Manchester Ctr Cellular Metab, Manchester, Lancs, England
[5] Austrian Acad Sci, Inst Mol Biotechnol, IMBA, A-1010 Vienna, Austria
[6] Danish Canc Soc, Res Ctr, Copenhagen, Denmark
[7] Palacky Univ, Inst Mol & Translat Med, Fac Med & Dent, CR-77147 Olomouc, Czech Republic
[8] Acad Athens, Biomed Res Fdn, Athens, Greece
关键词
p53; feedback loop; ARF; anti-tumor barrier; MKK7; senescence; Wip-1; p38; MAPK; replication stress; DNA damage response; ONCOGENE-INDUCED SENESCENCE; TUMOR-SUPPRESSOR PROTEIN; GENOMIC INSTABILITY; P53; PATHWAY; ACTIVATION; ATM; KINASE; STRESS; WIP1; PHOSPHORYLATION;
D O I
10.4161/cc.28654
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Sensing, integrating, and processing of stressogenic signals must be followed by accurate differential response(s) for a cell to survive and avoid malignant transformation. The DNA damage response (DDR) pathway is vital in this process, as it deals with genotoxic/oncogenic insults, having p53 as a nodal effector that performs most of the above tasks. Accumulating data reveal that other pathways are also involved in the same or similar processes, conveying also to p53. Emerging questions are if, how, and when these additional pathways communicate with the DDR axis. Two such stress response pathways, involving the MKK7 stress-activated protein kinase (SAPK) and ARF, have been shown to be interlocked with the ATM/ATR-regulated DDR axis in a highly ordered manner. This creates a new landscape in the DDR orchestrated response to genotoxic/oncogenic insults that is currently discussed.
引用
收藏
页码:1227 / 1236
页数:10
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