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Molecular and Cellular Biology, April 2002, p. 2147-2158, Vol. 22, No. 7
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.7.2147-2158.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Regulation of E2F1-Dependent Gene Transcription and Apoptosis by the ETS-Related Transcription Factor GABP{gamma}1

Ludger Hauck,1,2 Rudolf G. Kaba,2 Martin Lipp,2 Rainer Dietz,1,2 and Rüdiger von Harsdorf1,2*

Department of Cardiology, Campus Virchow Clinic, Charité, Humboldt University,1 Max Delbrück Center for Molecular Medicine, Berlin, Germany2

Received 26 November 2001/ Accepted 14 December 2001

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 GABP{gamma}1 in vitro and in vivo. The binding domain interacting with GABP{gamma}1 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 GABP{gamma}1 is restricted to E2F1. DNA-binding E2F1 complexes containing GABP{gamma}1 are characterized by enhanced E2F1-dependent transcriptional activity. Moreover, GABP{gamma}1 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.

* Corresponding author. Mailing address: Medizinische Klinik mit Schwerpunkt Kardiologie, Universitätsklinikum Charité, Humboldt-Universität zu Berlin, Augustenburger Platz 1, 13353 Berlin, Germany. Phone: 49-30-450 5537 47. Fax: 49-30-450 5539 77. E-mail: rharsdo{at}mdc-berlin.de.

Molecular and Cellular Biology, April 2002, p. 2147-2158, Vol. 22, No. 7
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.7.2147-2158.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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