A role for p53 in maintaining and establishing the quiescence growth arrest in human cells.

2.50
Hdl Handle:
http://hdl.handle.net/10541/82461
Title:
A role for p53 in maintaining and establishing the quiescence growth arrest in human cells.
Authors:
Itahana, Koji; Dimri, Goberdhan P; Hara, Eiji; Itahana, Yoko; Zou, Ying; Desprez, Pierre-Yves; Campisi, Judith
Abstract:
The p53 tumor suppressor protein induces transient growth arrest or apoptosis in response to genotoxic stress and mediates the irreversible growth arrest of cellular senescence. We present evidence here that p53 also contributes to the reversible, growth factor-dependent arrest of quiescence (G(0)). Microinjection of expression vectors encoding either MDM2 or a pRb-binding mutant of SV40 T antigen, both of which abrogate p53 function, stimulated quiescent normal human fibroblasts to initiate DNA synthesis and were 40-70% as effective as wild-type T antigen. Electrophoretic mobility shift and p53 transactivation assays showed that p53 activity was higher in quiescent and senescent cells compared with proliferating cells. As proliferating cells entered G(0) after growth factor withdrawal, the p53 mRNA level increased, followed by transient accumulation of the protein. Shortly thereafter, the expression (mRNA and protein) of p21, a p53 target gene and effector of cell cycle arrest, increased. Finally, stable expression of the HPV16 E6 oncogene or dominant negative p53 peptide, GSE-22, both of which inhibit p53 function, delayed entry into quiescence following growth factor withdrawal. Our data indicate that p53 is activated during both quiescence and senescence. They further suggest that p53 activity contributes, albeit not exclusively, to the quiescent growth arrest.
Affiliation:
Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.
Citation:
A role for p53 in maintaining and establishing the quiescence growth arrest in human cells. 2002, 277 (20):18206-14 J. Biol. Chem.
Journal:
The Journal of Biological Chemistry
Issue Date:
17-May-2002
URI:
http://hdl.handle.net/10541/82461
DOI:
10.1074/jbc.M201028200
PubMed ID:
11880381
Type:
Article
Language:
en
ISSN:
0021-9258
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorItahana, Koji-
dc.contributor.authorDimri, Goberdhan P-
dc.contributor.authorHara, Eiji-
dc.contributor.authorItahana, Yoko-
dc.contributor.authorZou, Ying-
dc.contributor.authorDesprez, Pierre-Yves-
dc.contributor.authorCampisi, Judith-
dc.date.accessioned2009-09-24T10:09:35Z-
dc.date.available2009-09-24T10:09:35Z-
dc.date.issued2002-05-17-
dc.identifier.citationA role for p53 in maintaining and establishing the quiescence growth arrest in human cells. 2002, 277 (20):18206-14 J. Biol. Chem.en
dc.identifier.issn0021-9258-
dc.identifier.pmid11880381-
dc.identifier.doi10.1074/jbc.M201028200-
dc.identifier.urihttp://hdl.handle.net/10541/82461-
dc.description.abstractThe p53 tumor suppressor protein induces transient growth arrest or apoptosis in response to genotoxic stress and mediates the irreversible growth arrest of cellular senescence. We present evidence here that p53 also contributes to the reversible, growth factor-dependent arrest of quiescence (G(0)). Microinjection of expression vectors encoding either MDM2 or a pRb-binding mutant of SV40 T antigen, both of which abrogate p53 function, stimulated quiescent normal human fibroblasts to initiate DNA synthesis and were 40-70% as effective as wild-type T antigen. Electrophoretic mobility shift and p53 transactivation assays showed that p53 activity was higher in quiescent and senescent cells compared with proliferating cells. As proliferating cells entered G(0) after growth factor withdrawal, the p53 mRNA level increased, followed by transient accumulation of the protein. Shortly thereafter, the expression (mRNA and protein) of p21, a p53 target gene and effector of cell cycle arrest, increased. Finally, stable expression of the HPV16 E6 oncogene or dominant negative p53 peptide, GSE-22, both of which inhibit p53 function, delayed entry into quiescence following growth factor withdrawal. Our data indicate that p53 is activated during both quiescence and senescence. They further suggest that p53 activity contributes, albeit not exclusively, to the quiescent growth arrest.en
dc.language.isoenen
dc.subjectTumour Suppressor Protein p53en
dc.subject.meshAntigens, Viral, Tumor-
dc.subject.meshCell Cycle-
dc.subject.meshCells, Cultured-
dc.subject.meshDNA Replication-
dc.subject.meshElectrophoresis, Polyacrylamide Gel-
dc.subject.meshFibroblasts-
dc.subject.meshG0 Phase-
dc.subject.meshHumans-
dc.subject.meshMicroinjections-
dc.subject.meshRNA, Messenger-
dc.subject.meshTranscriptional Activation-
dc.subject.meshTumor Suppressor Protein p53-
dc.titleA role for p53 in maintaining and establishing the quiescence growth arrest in human cells.en
dc.typeArticleen
dc.contributor.departmentLife Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.en
dc.identifier.journalThe Journal of Biological Chemistryen

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