Reference - Detail
RRC ID | 62146 |
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Author | Sugikawa E, Yazaki N, Tsunoda S, Nakanishi N, Ohashi M. |
Title | Inhibition of mutant p53 phosphorylation at serine 15 or serine 315 partially restores the function of wild-type p53. |
Journal | Biochem Biophys Res Commun |
Abstract |
The tumor suppressor protein p53 is a phosphoprotein and has growth and transformation suppression functions. Phosphorylation of wild-type p53 is known to modulate its function. To investigate the role of phosphorylation in modulating the functions of mutant p53, we constructed a series of phosphorylation site mutants based on mutant p53 Ala143 (p53-143) and p53 His175 (p53-175). When transfected into p53-negative Saos-2 cells, parental mutant p53-143 and p53-175 abolished both growth suppression and induction of apoptosis. However, DNA-activated protein kinase (DNA-PK) or cyclin-dependent kinase (cdks) phosphorylation site double mutants partially restored the growth suppression and induction of apoptosis and recovered the p53-specific DNA binding activity. We also observed a difference in sensitivity to calpain from parental mutants p53-175 and p53-175/15 or p53-175/315. These results suggest that the lack of phosphorylation at either the DNA-PK or cdks site in p53 mutants partially restores the wild-type functions by altering their conformation. |
Volume | 261(2) |
Pages | 256-63 |
Published | 1999-8-2 |
DOI | 10.1006/bbrc.1999.1019 |
PII | S0006-291X(99)91019-7 |
PMID | 10425175 |
MeSH | Apoptosis / genetics Base Sequence Binding Sites / genetics Calpain / pharmacology Cell Division / genetics Cell Line Cyclin-Dependent Kinases / metabolism DNA / metabolism DNA Primers / genetics DNA-Activated Protein Kinase DNA-Binding Proteins* Humans Nuclear Proteins Phosphorylation Point Mutation* Protein Serine-Threonine Kinases / metabolism Serine / metabolism Transfection Tumor Suppressor Protein p53 / chemistry Tumor Suppressor Protein p53 / genetics* Tumor Suppressor Protein p53 / metabolism* |
IF | 2.985 |
Resource | |
Human and Animal Cells | Saos-2(RCB0428) |