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PMID: 12604789 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

The role of E2F4 in adipogenesis is independent of its cell cycle regulatory activity.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 100 ·No. 5 ·2003-03-04 ·Pages 2456-61

Landsberg RL, Sero JE, Danielian PS, Yuan TL, Lee EY, Lees JA

Abstract

The E2F and pocket protein families are known to play an important role in the regulation of both cellular proliferation and terminal differentiation. In this study, we have used compound E2F and pocket protein mutant mouse embryonic fibroblasts to dissect the role of these proteins in adipogenesis. This analysis shows that loss of E2F4 allows cells to undergo spontaneous differentiation. The ability of E2F4 to prevent adipogenesis seems to be quite distinct from the known properties of E2F. First, it can be separated from any change in either E2F-responsive gene expression or cell cycle regulation. Second, it is a specific property of E2F4, and not other E2Fs, and it occurs independently of E2F4's ability to interact with pocket proteins. In addition, E2F4 loss does not override the differentiation defect resulting from pRB loss even though it completely suppresses the proliferation defect of Rb(-/-) mouse embryonic fibroblasts. This finding definitively separates the known, positive role of pRB in adipogenesis from its cell cycle function and shows that this pocket protein is required to act downstream of E2F4 in the differentiation process.

MeSH Terms
Adipocytes/cytology,metabolism Animals Azo Compounds/pharmacology Blood Proteins/metabolism CCAAT-Enhancer-Binding Protein-alpha/metabolism Cell Cycle Cell Differentiation Cell Division DNA-Binding Proteins/chemistry,physiology E2F4 Transcription Factor Fibroblasts/metabolism Genotype Immunoblotting Mice Nuclear Proteins/metabolism Protein Binding Proteins Receptors, Cytoplasmic and Nuclear/metabolism Retinoblastoma Protein/metabolism Retinoblastoma-Like Protein p107 Retinoblastoma-Like Protein p130 Time Factors Transcription Factors/chemistry,metabolism,physiology
Chemicals
Azo Compounds Blood Proteins CCAAT-Enhancer-Binding Protein-alpha DNA-Binding Proteins E2F4 Transcription Factor Nuclear Proteins Proteins Rbl1 protein, mouse Rbl2 protein, mouse Receptors, Cytoplasmic and Nuclear Retinoblastoma Protein Retinoblastoma-Like Protein p107 Retinoblastoma-Like Protein p130 Transcription Factors oil red O
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Landsberg Rebecca L
Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Sero Julia E
Danielian Paul S
Yuan Tina L
Lee Eunice Y
Lees Jacqueline A
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0138064100
Published
2003-03-04
Epub
2003-00-25
Pages
2456-61
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC151362
Subset
IM
Grants
NIGMS NIH HHS · R01 GM053204 · United States
NIGMS NIH HHS · R01-GM53204 · United States
External Links
PubMed source DOI: 10.1073/pnas.0138064100 PMC Full Text View journal details
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