Accession Number:

ADA601038

Title:

The Role of Skp1-Cul1-F-box Ubiquitin Ligases in Src-Stimulated Estrogen Receptor Proteolysis and Estrogen Receptor Target Gene Expression

Descriptive Note:

Annual summary 1 Jan 2011-31 Dec 2013

Corporate Author:

MIAMI UNIV FL

Personal Author(s):

Report Date:

2014-03-01

Pagination or Media Count:

86.0

Abstract:

Estrogen triggers transactivation coupled estrogen receptor ER proteolysis, but mechanisms thereof remain obscure. Present data link estrogenER -driven transcription with cell cycle progression. Here, we identify SKP2 as a late-acting coactivator that drives ER targets to promote G1-to-S progression. Data support a model in which estrogen-activated ER phosphorylation, to prime ER -SCFSKP2 binding in late G1. SKP2 activates ER ubiquitylation and proteolysis. Putative late ER targets were identified by expression profiling. SKP2 knockdown attenuated E2F-1 and BLM induction. SKP2 overexpression enhanced estrogen-induced E2F-1 and BLM expression. SKP2 knockdown impaired estrogen-stimulated ER , SKP2, SRC3 and RNA polymerase II recruitment to E2F-1 and BLM promoters. SKP2 serves as dual ER E3 ligasecoactivator for late-activated target genes, revealing a novel mechanism whereby ER SCFSKP2 transactivation of E2F-1 feeds forward to drive G1-to-S.

Subject Categories:

  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE