EGR1 Target Genes That Regulate Growth/Survival of Prostate Cells
Abstract
Related co-activators p3OO and CBP, affect the transcriptional activities of many transcription factors (TF), producing multiple downstream effects. I have shown that the immediate early response TF, Egr1, acts upstream of p3OO/CBP to induce or to repress transcription, depending on stimulus. Cells induced with serum to increase endogenous Egr1, increase the transcription of p3OO/CBP, only when Egr1 binding sites in the promoter are not mutated, causing the expression of downstream targets of Egr1 leading to survival. Induction of p3OO/CBP by Egr1, results in acetylation and stabilization of Egr1 and transactivation of survival genes but repression of Egr1 and p3OO/CBP in negative feedback loops. In contrast, induction of Egr1 by UV-C irradiation leads to repression of p3OO/CBP transcription: Egr1 is preferentially phosphorylated, leading to regulation of target genes that cause cell death. This complex balance of opposing effects appears to finely modulate important cellular life and death responses. I have shown that serum stimulation of prostate cells results in cell growth by the up-regulation of p3OO/CBP. In contrast, the stimulus of ultraviolet irradiation leads to cell cycle block and apoptosis through the inhibition of p3OO/CBP.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2004
- Accession Number
- ADA425989
Entities
People
- Jianxiu Yu
Organizations
- Sanford Burnham Prebys Medical Discovery Institute