The role of DNA damage responses in p53 biology
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- 作者：Daniel Speidel (1) (2)
1. Children鈥檚 Medical Research Institute ; 214 Hawkesbury Road ; Westmead ; NSW ; 2145 ; Australia
2. Sydney Medical School ; The University of Sydney ; Sydney ; NSW ; 2006 ; Australia - 关键词：P53 ; DNA damage ; Tumour suppression ; Cancer therapy ; Apoptosis ; Cell cycle arrest ; Senescence ; DNA Repair
- 刊名：Archives of Toxicology
- 出版年：2015
- 出版时间：April 2015
- 年：2015
- 卷：89
- 期：4
- 页码：501-517
- 全文大小：497 KB
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- 出版者：Springer Berlin Heidelberg
- ISSN：1432-0738
文摘
The tumour suppressor p53 is a central player in cellular DNA damage responses. P53 is upregulated and activated by genotoxic stress and induces a transcriptional programme with effectors promoting apoptosis, cell cycle arrest, senescence and DNA repair. For the best part of the last three decades, these DNA damage-related programmes triggered by p53 were unequivocally regarded as the major if not sole mechanism by which p53 exerts its tumour suppressor function. However, this interpretation has been challenged by a number of recent in vivo studies, demonstrating that mice which are defective in inducing p53-dependent apoptosis, cell cycle arrest and senescence suppress thymic lymphoma as well as wild-type p53 expressing animals. Consequently, the importance of DNA damage responses for p53-mediated tumour suppression has been questioned. In this review, I summarize current knowledge on p53-controlled DNA damage responses and argue that these activities, while their role has certainly changed, remain an important feature of p53 biology with relevance for cancer therapy and tumour suppression.