Regulation of E2F1-Dependent Gene Transcription and Apoptosis by the ETS-Related Transcription Factor GABPγ1

Abstract

The E2F family of transcription factors comprises six related members which are involved in the control of the coordinated progression through the G₁/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 GABPγ1 in vitro and in vivo. The binding domain interacting with GABPγ1 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 GABPγ1 is restricted to E2F1. DNA-binding E2F1 complexes containing GABPγ1 are characterized by enhanced E2F1-dependent transcriptional activity. Moreover, GABPγ1 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.

We are indebted to H. Handa (Tokyo Institute of Technology, Yokohama, Japan), who generously provided GABP cDNAs and antibodies to GABP, and to K. Vousden, National Cancer Institute, Frederick, Md., for her kind gift of mutant E2F1 plasmids.

This work was supported in part by a grant-in-aid from the Max Delbrück Center (M.L. and R.V.H.).