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

Akira Kurihara, Hirokazu Nagoshi, Masato Yabuki, Ryuhei Okuyama, Masuo Obinata, Shuntaro Ikawa

研究成果: Article査読

21 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)853-861
ページ数9
ジャーナルGenes to Cells
12
7
DOI
出版ステータスPublished - 2007 7

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

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