期刊
CANCER LETTERS
卷 400, 期 -, 页码 30-36出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2017.04.030
关键词
RASSF; HIPK2; PP1A; Retinoblastoma; p53; Ras
类别
资金
- National Institutes of Health [R01 CA133171-01A2]
- Wistar Institute T32 Training Grant [T32 CA09171]
The Ras genes are the most frequently mutated oncogenes in human cancer. However, Ras biology is quite complex. While Ras promotes tumorigenesis by regulating numerous growth promoting pathways, activated Ras can paradoxically also lead to cell cycle arrest, death, and Oncogene-Induced Senescence (OIS). OIS is thought to be a critical pathway that serves to protect cells against aberrant Ras signaling. Multiple reports have highlighted the importance of the p53 and Rb tumor suppressors in Ras mediated OIS. However, until recently, the molecular mechanisms connecting Ras to these proteins remained unknown. The RASSF family of tumor suppressors has recently been identified as direct effectors of Ras. One of these members, NORE1A (RASSF5), may be the missing link between Ras-induced senescence and the regulation of p53 and Rb. This occurs both quantitatively, by promoting protein stability, as well as qualitatively via promoting critical pro-senescent post-translational modifications. Here we review the mechanisms by which NORE1A can activate OIS as a barrier against Ras-mediated transformation, and how this could lead to improved therapeutic strategies against cancers having lost NORE1A expression. (C) 2017 Elsevier B.V. All rights reserved.
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