The role of E2F4 in adipogenesis is independent of its cell cycle regulatory activity.
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.
Landsberg
Rebecca L
RL
Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Sero
Julia E
JE
Danielian
Paul S
PS
Yuan
Tina L
TL
Lee
Eunice Y
EY
Lees
Jacqueline A
JA
D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D000818:Animals; D001391:Azo Compounds / Q000494:pharmacology; D001798:Blood Proteins / Q000378:metabolism; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000378:metabolism; D002453:Cell Cycle; D002454:Cell Differentiation; D002455:Cell Division; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000502:physiology*; D050704:E2F4 Transcription Factor; D005347:Fibroblasts / Q000378:metabolism; D005838:Genotype; D015151:Immunoblotting; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism; D011485:Protein Binding; D011506:Proteins; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism; D050720:Retinoblastoma-Like Protein p107; D050717:Retinoblastoma-Like Protein p130; D013997:Time Factors; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*
D001391:Azo Compounds; D001798:Blood Proteins; D022763:CCAAT-Enhancer-Binding Protein-alpha; D004268:DNA-Binding Proteins; D050704:E2F4 Transcription Factor; D009687:Nuclear Proteins; D011506:Proteins; C489485:Rbl1 protein, mouse; C493838:Rbl2 protein, mouse; D018160:Receptors, Cytoplasmic and Nuclear; D016160:Retinoblastoma Protein; D050720:Retinoblastoma-Like Protein p107; D050717:Retinoblastoma-Like Protein p130; D014157:Transcription Factors; C011049:oil red O