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Genes to Cells (2007) 12, 853-861. doi:10.1111/j.1365-2443.2007.01097.x
© 2007 Blackwell Publishing or its licensors

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Ser46 phosphorylation of p53 is not always sufficient to induce apoptosis: multiple mechanisms of regulation of p53-dependent apoptosis

Akira Kurihara1,2,3, Hirokazu Nagoshi1, Masato Yabuki1,2,3, Ryuhei Okuyama4, Masuo Obinata2,3 and Shuntaro Ikawa1,2,3,*

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.


Communicated by: Tadashi Yamamoto

* Correspondence: E-mail: sikawa{at}cir.tohoku.ac.jp







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