Interaction of estrogen receptor alpha with proliferating cell nuclear antigen

摘要

The ability of estrogen receptor alpha (ER alpha) to modulate gene expression is influenced by the recruitment of a host of co-regulatory proteins to target genes. To further understand how estrogen-responsive genes are regulated, we have isolated and identified proteins associated with ERa when it is bound to DNA containing the consensus estrogen response element ( ERE). One of the proteins identified in this complex, proliferating cell nuclear antigen ( PCNA), is required for DNA replication and repair. We show that PCNA interacts with ERa in the absence and in the presence of DNA, enhances the interaction of ERa with ERE-containing DNA, and associates with endogenous estrogen-responsive genes. Interestingly, rather than altering hormone responsiveness of endogenous, estrogen-responsive genes, PCNA increases the basal expression of these genes. Our studies suggest that in addition to serving as a platform for the recruitment of DNA replication and repair proteins, PCNA may serve as a platform for transcription factors involved in regulating gene expression.