Functional interaction between E2F-4 and p130: evidence for distinct mechanisms underlying growth suppression by different retinoblastoma protein family members.
Little is known of the mechanisms controlling the G0/G1 transition of the cell cycle. The induction of immediate early gene expression, thought to be important for this process, suggests that the key factors controlling this transition preexist in quiescent cells. The E2F family of transcription factors likely play an important role in this process, because E2F DNA-binding activity exists in quiescent cells, and the induction of at least some immediate early genes requires intact E2F regulatory promoter sites. Here, we show that the major G0 E2F activity of primary human T cells, E2F-4, is stably bound to the p130 pocket protein in association with a DP heterodimerization partner. p130-E2F-4 binding has functional implications because p130 effectively suppressed E2F-4-mediated trans-activation, and coexpression of E2F4 overcame p130-mediated G1 arrest more efficiently than RB-induced G1 blockade. Conversely, E2F-1 overrode an RB-induced G1 block more efficiently than E2F-4. Thus, p130 and RB appear to induce cell cycle arrest via biochemically distinct mechanisms that involve different E2F family members.
Vairo
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Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Livingston
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DM
Ginsberg
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D004268:DNA-Binding Proteins / Q000378:metabolism*; D050704:E2F4 Transcription Factor; D016193:G1 Phase / Q000502:physiology; D006131:Growth Inhibitors / Q000378:metabolism*; D006801:Humans; D010750:Phosphoproteins; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism*; D016192:Resting Phase, Cell Cycle / Q000502:physiology; D016160:Retinoblastoma Protein / Q000378:metabolism*; D050717:Retinoblastoma-Like Protein p130; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D050704:E2F4 Transcription Factor; D006131:Growth Inhibitors; D010750:Phosphoproteins; D011506:Proteins; C493837:RBL2 protein, human; D016160:Retinoblastoma Protein; D050717:Retinoblastoma-Like Protein p130; D014157:Transcription Factors