The Role of Phosphorylation in IR-induced p53 Stabilization and Activation
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Accession number;06A0107592
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| Title;The Role of Phosphorylation in IR-induced p53 Stabilization and Activation |
| Author;
YAMAUCHI MOTOHIRO
(Nagasaki Univ., Nagasaki, Jpn)
SUZUKI KEIJI
(Nagasaki Univ., Nagasaki, Jpn)
KODAMA SEIJI
(Osaka Prefecture Univ., Sakai, Jpn)
WATANABE MASAMI
(Kyoto Univ., Kumatori, Jpn)
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Journal Title;Acta Med Nagasaki Ensia
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Journal Code:X0952A
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ISSN:0001-6055
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VOL.50;NO.Supplement 1;PAGE.51-54(2005)
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| Figure&Table&Reference;REF.25 |
| Pub. Country;Japan |
| Language;English |
| 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. (author abst.) |
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