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PMID: 9271121 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

PPARgamma induces cell cycle withdrawal: inhibition of E2F/DP DNA-binding activity via down-regulation of PP2A.

Genes & development ·Vol. 11 ·No. 15 ·1997-08-01 ·Pages 1987-98

Altiok S, Xu M, Spiegelman BM

Abstract

PPAR gamma is an adipose-selective nuclear hormone receptor that plays a key role in the control of adipocyte differentiation. Previous studies indicated that activation of ectopically expressed PPAR gamma induces differentiation when cells have ceased growth because of confluence. We show here that ligand activation of PPAR gamma is sufficient to induce growth arrest in fibroblasts and SV40 large T-antigen transformed, adipogenic HIB1B cells. Cell cycle withdrawal is accompanied by a decrease in the DNA-binding and transcriptional activity of the E2F/DP complex, which is attributable to an increase in the phosphorylation of these proteins, especially DP-1. This effect is a consequence of decreased expression of the catalytic subunit of the serine-threonine phosphatase PP2A. These data suggest an important role for PP2A in the control of E2F/DP activity and a new mode of cell cycle control in differentiation.

MeSH Terms
3T3 Cells Adipocytes/cytology Animals Carrier Proteins Cell Cycle/physiology Cell Cycle Proteins Cell Line, Transformed DNA-Binding Proteins/metabolism E2F Transcription Factors Ligands Mice Phosphoprotein Phosphatases/metabolism Phosphorylation Pioglitazone RNA, Messenger/analysis Receptors, Cytoplasmic and Nuclear/genetics,physiology Retinoblastoma-Binding Protein 1 Thiazoles/pharmacology Thiazolidinediones Transcription Factor DP1 Transcription Factors/genetics,metabolism,physiology
Chemicals
Arid4a protein, mouse Carrier Proteins Cell Cycle Proteins DNA-Binding Proteins E2F Transcription Factors Ligands RNA, Messenger Receptors, Cytoplasmic and Nuclear Retinoblastoma-Binding Protein 1 Tfdp1 protein, mouse Thiazoles Thiazolidinediones Transcription Factor DP1 Transcription Factors Phosphoprotein Phosphatases Pioglitazone
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Altiok S
Dana-Farber Cancer Institute and the Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Xu M
Spiegelman B M
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.11.15.1987
Published
1997-08-01
Pages
1987-98
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC316411
Subset
IM
Grants
NIDDK NIH HHS · DK31405 · United States
External Links
PubMed source DOI: 10.1101/gad.11.15.1987 PMC Full Text View journal details
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