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1 Center for Interdisciplinary Research, Tohoku University, Aramaki, 6-3 Aoba, Aoba-ku, Sendai, Japan 980-8578
2
Department of Cell Biology, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai, Japan 980-8575
3
Laboratory of Cell Differentiation, Graduate School of Life Sciences, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai, Japan 980-8575
4
Department of Dermatology, Tohoku University, Graduate School of Medicine, 2-1 Seiryo-mach, Aoba-ku, Sendai, Japan 980-8574
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 (Ser46) 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 Ser46 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 Ser46, we showed that Ser46 phosphorylation is not a prerequisite for induction of the proapoptotic gene AIP1. These results indicate that Ser46 phosphorylation of p53 is not required for ADR-induced apoptosis.
* Correspondence: E-mail: sikawa{at}cir.tohoku.ac.jp
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