role of p53 in cell death and human cancersp53在细胞死亡和人类癌症的作用.pdfVIP

Cancers 2011, 3, 994-1013; doi:10.3390/cancers3010994 OPEN ACCESS cancers ISSN 2072-6694 /journal/cancers Review Role of p53 in Cell Death and Human Cancers Toshinori Ozaki 1 and Akira Nakagawara 2,* 1 Laboratory of Anti-tumor Research, Chiba Cancer Center Research Institute, 666-2 Nitona, Chuoh-ku, Chiba 260-8717, Japan; E-Mail: tozaki@chiba-cc.jp 2 Division of Biochemistry and Laboratory of Innovative Cancer Therapeutics, Chiba Cancer Center Research Institute, 666-2 Nitona, Chuoh-ku, Chiba 260-8717, Japan * Author to whom correspondence should be addressed; E-Mail: akiranak@chiba-cc.jp; Tel.: +81-43-264-5431; Fax: +81-43-265-4459. Received: 7 December 2010; in revised form: 22 February 2011 / Accepted: 22 February 2011 / Published: 3 March 2011 Abstract: p53 is a nuclear transcription factor with a pro-apoptotic function. Since over 50% of human cancers carry loss of function mutations in p53 gene, p53 has been considered to be one of the classical type tumor suppressors. Mutant p53 acts as the dominant-negative inhibitor toward wild-type p53. Indeed, mutant p53 has an oncogenic potential. In some cases, malignant cancer cells bearing p53 mutations display a chemo-resistant phenotype. In response to a variety of cellular stresses such as DNA damage, p53 is induced to accumulate in cell nucleus to exert its pro-apoptotic function. Activated p53 promotes cell cycle arrest to allow DNA repair and/or apoptosis to prevent