Open AccessThe cell death machinery governed by the p53 tumor suppressor in response to DNA damage
Author(s) -
Yoshida Kiyotsugu,
Miki Yoshio
Publication year - 2010
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2009.01488.x
Subject(s) - dna damage , apoptosis , suppressor , microbiology and biotechnology , dna repair , biology , programmed cell death , cell fate determination , tumor suppressor gene , cell cycle , cell cycle checkpoint , cell , dna , cancer research , function (biology) , gene , genetics , carcinogenesis , transcription factor
The cellular response to genotoxic stress that damages DNA includes cell cycle arrest, activation of DNA repair, and in the event of irreparable damage, induction of apoptosis. However, the signals that determine cell fate, that is, survival or apoptosis, are largely unclear. The tumor suppressor p53 has been implicated in many important cellular processes, including regulation of apoptotic cell death. When cells encounter genotoxic stress, certain sensors for DNA lesions eventually stabilize and activate p53. Subsequently, p53 exerts its tumor suppressor function by transactivating numerous target genes. Active p53 is subjected to a complex and diverse array of covalent post‐translational modifications, which selectively influence the expression of p53 target genes. In this regard, the molecular basis for how p53 induces apoptosis has been extensively studied; however, the relative contribution of each downstream effecter is still to be explored. Moreover, little is known about precise mechanisms by which modified p53 is capable of apoptosis induction. A thorough understanding for the whole picture of p53 modification in apoptosis will be extremely valuable in the development of highly effective and specific therapies for caner patients. This review is focused on the current views regarding the regulation of cell fate by p53 in the apoptotic response to DNA damage. ( Cancer Sci 2010; 101: 831–835)