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Ser 46 phosphorylation of p53 is not always sufficient to induce apoptosis: multiple mechanisms of regulation of p53‐dependent apoptosis
Author(s) -
Kurihara Akira,
Nagoshi Hirokazu,
Yabuki Masato,
Okuyama Ryuhei,
Obinata Masuo,
Ikawa Shuntaro
Publication year - 2007
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/j.1365-2443.2007.01097.x
Subject(s) - phosphorylation , apoptosis , biology , transactivation , microbiology and biotechnology , programmed cell death , gene , gene expression , biochemistry
The tumor suppressor gene p53 plays a central role in determining cell fate in response to DNA damage; cells may undergo either senescence or apoptosis, depending on cell type. Phosphorylation of Serine 46 (Ser 46 ) of p53 is considered to be a primary determinant for the induction of apoptosis, by selectively inducing transactivation of p53 target genes that have proapoptotic function. However, the generality of this mechanism of regulation of p53 remains a matter of debate. We investigated the role of p53 phosphorylation in adriamycin (ADR)‐induced apoptosis. We found that Ser 46 was phosphorylated in four different cell lines undergoing ADR‐induced senescence, as well as in two different cell lines undergoing ADR‐induced apoptosis. Using alanine and glutamic acid substitution mutants of p53 Ser 46 , we showed that Ser 46 phosphorylation is not a prerequisite for induction of the proapoptotic gene AIP1 . These results indicate that Ser 46 phosphorylation of p53 is not required for ADR‐induced apoptosis.