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Transcriptional regulation of human survivin by early growth response (Egr)-1 transcription factor

Item Type:Article
Title:Transcriptional regulation of human survivin by early growth response (Egr)-1 transcription factor
Creators Name:Wagner, M. and Schmelz, K. and Doerken, B. and Tamm, I.
Abstract: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.
Keywords:Survivin, Egr-1, Transcription, Apoptosis
Source:International Journal of Cancer
Publisher:Wiley (U.S.A.)
Page Range:1278-1287
Date:15 March 2008
Official Publication:https://doi.org/10.1002/ijc.23183
PubMed:View item in PubMed

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