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PMID: 9732264 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

JNK targets p53 ubiquitination and degradation in nonstressed cells.

Genes & development ·Vol. 12 ·No. 17 ·1998-09-01 ·Pages 2658-63

Fuchs SY, Adler V, Buschmann T, Yin Z, Wu X, Jones SN, Ronai Z

Abstract

In this study we elucidated the role of nonactive JNK in regulating p53 stability. The amount of p53-JNK complex was inversely correlated with p53 level. A peptide corresponding to the JNK binding site on p53 efficiently blocked ubiquitination of p53. Similarly, p53 lacking the JNK binding site exhibits a longer half-life than p53(wt). Outcompeting JNK association with p53 increased the level of p53, whereas overexpression of a phosphorylation mutant form of JNK inhibited p53 accumulation. JNK-p53 and Mdm2-p53 complexes were preferentially found in G0/G1 and S/G2M phases of the cell cycle, respectively. Altogether, these data indicate that JNK is an Mdm2-independent regulator of p53 stability in nonstressed cells.

MeSH Terms
3T3 Cells Amino Acid Sequence Animals Calcium-Calmodulin-Dependent Protein Kinases/chemistry,metabolism Cell Line JNK Mitogen-Activated Protein Kinases Mice Mitogen-Activated Protein Kinases Molecular Sequence Data Nuclear Proteins Peptide Fragments/chemistry,metabolism Phosphorylation Proto-Oncogene Proteins/metabolism Proto-Oncogene Proteins c-mdm2 Recombinant Proteins/chemistry,metabolism Reticulocytes/metabolism Sequence Deletion Spodoptera Transfection Tumor Suppressor Protein p53/chemistry,metabolism Ubiquitins/metabolism
Chemicals
Nuclear Proteins Peptide Fragments Proto-Oncogene Proteins Recombinant Proteins Tumor Suppressor Protein p53 Ubiquitins Mdm2 protein, mouse Proto-Oncogene Proteins c-mdm2 Calcium-Calmodulin-Dependent Protein Kinases JNK Mitogen-Activated Protein Kinases Mitogen-Activated Protein Kinases
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Fuchs S Y
The Ruttenberg Cancer Center, Mount Sinai School of Medicine, New York, New York 10029, USA.
Adler V
Buschmann T
Yin Z
Wu X
Jones S N
Ronai Z
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.12.17.2658
Published
1998-09-01
Pages
2658-63
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC317120
Subset
IM
Grants
NCI NIH HHS · CA59908 · United States
NCI NIH HHS · CA78419 · United States
External Links
PubMed source DOI: 10.1101/gad.12.17.2658 PMC Full Text View journal details
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