Regulation of E2F1-dependent gene transcription and apoptosis by the ETS-related transcription factor GABPgamma1.
The E2F family of transcription factors comprises six related members which are involved in the control of the coordinated progression through the G(1)/S-phase transition of cell cycle or in cell fate decision. Their activity is regulated by pocket proteins, including pRb, p107, and p130. Here we show that E2F1 directly interacts with the ETS-related transcription factor GABPgamma1 in vitro and in vivo. The binding domain interacting with GABPgamma1 was mapped to the C-terminal amino acids 310 to 437 of E2F1, which include its transactivation and pRb binding domain. Among the E2F family of transcription factors, the interaction with GABPgamma1 is restricted to E2F1. DNA-binding E2F1 complexes containing GABPgamma1 are characterized by enhanced E2F1-dependent transcriptional activity. Moreover, GABPgamma1 suppresses E2F1-dependent apoptosis by mechanisms other than the inhibition of the transactivation capacity of E2F1. In summary, our results provide evidence for a novel pRb-independent mechanism regulating E2F1-dependent transcription and apoptosis.
Hauck
Ludger
L
Department of Cardiology, Campus Virchow Clinic, Charité, Humboldt University, Germany.
Kaba
Rudolf G
RG
Lipp
Martin
M
Dietz
Rainer
R
von Harsdorf
Rüdiger
R
D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D018797:Cell Cycle Proteins; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D024202:Electrophoretic Mobility Shift Assay; D005434:Flow Cytometry; D051268:GA-Binding Protein Transcription Factor; D005786:Gene Expression Regulation; D006801:Humans; D020287:In Situ Nick-End Labeling; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics*; D020798:Two-Hybrid System Techniques
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D051268:GA-Binding Protein Transcription Factor; D012097:Repressor Proteins; D014157:Transcription Factors