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) : Zhou, Wen


Full Text : http://www.dtic.mil/dtic/tr/fulltext/u2/a601038.pdf


Report Date : Mar 2014


Pagination or Media Count : 86


Abstract : Estrogen triggers transactivation coupled estrogen receptor (ER ) proteolysis, but mechanisms thereof remain obscure. Present data link estrogen:ER -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 ligase/coactivator for late-activated target genes, revealing a novel mechanism whereby ER /SCFSKP2 transactivation of E2F-1 feeds forward to drive G1-to-S.


Descriptors :   *ESTROGENS , BREAST CANCER , GENE EXPRESSION , MOLECULES , PEPTIDE HYDROLASES


Subject Categories : Anatomy and Physiology
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE