Transcriptional regulation of human survivin by early growth response (Egr)-1 transcription factor
Article first published online: 20 NOV 2007
Copyright © 2007 Wiley-Liss, Inc.
International Journal of Cancer
Volume 122, Issue 6, pages 1278–1287, 15 March 2008
How to Cite
Wagner, M., Schmelz, K., Dörken, B. and Tamm, I. (2008), Transcriptional regulation of human survivin by early growth response (Egr)-1 transcription factor. Int. J. Cancer, 122: 1278–1287. doi: 10.1002/ijc.23183
- Issue published online: 21 JAN 2008
- Article first published online: 20 NOV 2007
- Manuscript Accepted: 24 AUG 2007
- Manuscript Received: 10 MAY 2007
- Deutsche José Carreras Leukämie-Stiftung. Grant Number: DJCLS-F05/08
- Deutsche Forschungsgemeinschaft
Survivin, a member of the inhibitor of apoptosis protein family, is involved in both, inhibition of apoptosis and regulation of cell division. Because of the tumor-specific expression of survivin, the reduction of its expression is an important therapeutic option in the treatment of malignant diseases. Thus, we analyzed the transcriptional regulation of survivin in order to establish survivin as a target gene for new therapeutic approaches. Here, we describe a novel regulatory region within the survivin promoter. After treatment with phorbol 12-myristate-13-acetate, the early growth response (Egr)-1 transcription factor binds to the sequence 5′GAGGGGGCG 3′ within the human survivin promoter in vitro and in entire cells. In reporter-gene assays and overexpression experiments, survivin is downregulated following exogenous expression of wildtype Egr-1. Using p53 wildtype and mutated cell lines, we show that Egr-1 negatively regulates survivin expression and sensitizes cell lines to TRAIL-induced apoptosis. © 2007 Wiley-Liss, Inc.