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The Role of Phosphorylation in IR-induced p53 Stabilization and Activation

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Title: The Role of Phosphorylation in IR-induced p53 Stabilization and Activation
Authors: Yamauchi, Motohiro / Suzuki, Keiji / Kodama, Seiji / Watanabe, Masami
Issue Date: Dec-2005
Citation: Acta medica Nagasakiensia. 2005, 50(supl.1), p.51-54
Abstract: It is well established that tumor suppressor p53 protein is stabilized and activated as a sequence-specific transcriptional factor in response to genotoxic stresses, including ionizing radiation (IR). Previous studies demonstrated that p53 is phosphorylated at N-terminal serines and a threonine after IR. Here, we examined the role of the phosphorylation, especially at Ser15, Thr18, and Ser20, in IR-induced p53 stabilization and activation, using alanine-substituted p53 at phosphorylation site (s). In the present study, we examined p53 stabilization and activation in two different cell lines : stabilization in HT1080-derived clone in which endogenous wild-type p53 was confirmed to be normally stabilized after IR; activation in p53-null H1299-derived clone in which ectopically-expressed p53 levels did not change before and after IR, because the increase in p53 levels affects transactivation by p53. In Western blot analysis and immunofluorescence staining, alanine-substituted p53 at Ser15, Thr18, and/or Ser20 was stabilized in the nucleus comparably with wild-type p53 2 h after 4 Gy of X-rays. However, Ser15-alanine-substituted p53 did not induce the expression of p21 protein, one of the p53-targeted gene products, after IR. These results indicate that phosphorylation at Ser15, Thr18, and Ser20 is not required for IR-induced p53 stabilization, however, Ser15-phosphorylation plays a role in IR-induced p21 induction by p53.
Keywords: p53 / Phosphorylation / Stabilization / Activation
URI: http://hdl.handle.net/10069/9312
ISSN: 00016055
Relational Links: http://joi.jlc.jst.go.jp/JST.JSTAGE/amn/50.S51
Type: Departmental Bulletin Paper
Text Version: publisher
Appears in Collections:Volume 50, No. supl.1

Citable URI : http://hdl.handle.net/10069/9312

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