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Cited by 303

The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.

ATM Mediates Phosphorylation at Multiple p53 Sites, Including Ser46, in Response to Ionizing Radiation

Open access
Saito, Shin'ichi, Goodarzi, Aaron A., Higashimoto, Yuichiro, Noda, Yuka, Lees-Miller, Susan P., Appella, Ettore, Anderson, Carl W.·2002·Journal of Biological Chemistry

Abstract

The p53 tumor suppressor protein preserves genome integrity by regulating growth arrest and apoptosis in response to DNA damage. In response to ionizing radiation (IR), ATM, the gene product mutated in ataxia telangiectasia, stabilizes and activates p53 through phosphorylation of Ser(15) and (indirectly) Ser(20). Here we show that phosphorylation of p53 on Ser(46), a residue important for p53 apoptotic activity, as well as on Ser(9), in response to IR also is dependent on the ATM protein kinase. IR-induced phosphorylation at Ser(46) was inhibited by wortmannin, a phosphatidylinositol 3-kinase inhibitor, but not PD169316, a p38 MAPK inhibitor. p53 C-terminal acetylation at Lys(320) and Lys(382), which may stabilize p53 and activate sequence-specific DNA binding, required Ser(15) phosphorylation by ATM and was enhanced by phosphorylation at nearby residues including Ser(6), Ser(9), and Thr(18). These observations, together with the proposed role of Ser(46) phosphorylation in mediating apoptosis, suggest that ATM is involved in the initiation of p53-dependent apoptosis after IR in human lymphoblastoid cells.

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Metadata

Authors
Saito, S., Goodarzi, A. A., Higashimoto, Y., Noda, Y., Lees-Miller, S. P., Appella, E., & Anderson, C. W.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2002-04
Volume
277
Issue
15
Pages
12491-12494
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2005236007
Cited by
303
References
8
FWCI
9.19
Type
journal article
Language
en
Open access
hybrid

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