Linked Life Data

15558026

Source:http://linkedlifedata.com/resource/pubmed/id/15558026

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2005-1-28
pubmed:abstractText
Regulation of nuclear receptor activity is the focus of numerous ongoing studies to develop novel therapies for the treatment of hormone-related cancer. Although cyclin D1 functions to control the activity of several nuclear receptors, the region(s) of the protein responsible for such transcriptional comodulation remain poorly defined. Herein, we map the region of cyclin D1 required for binding and repression of the androgen receptor (AR) to a central, exclusively alpha-helical domain. Deletion of this domain disrupted AR binding and corepressor activity. Further investigations showed that this domain is sufficient for AR interaction and possesses the ability to bind histone deacetylase 3. Strikingly, overexpression of this repressor region attenuates cell cycle progression in prostatic adenocarcinoma cells. The requirement of this domain for nuclear receptor repression was conserved with respect to thyroid hormone receptor beta-1, whereas cyclin D1 activation of the estrogen receptor occurred independently of the central region. Together, these data identify a minimal repression module within cyclin D1 and demonstrate that the coactivator and corepressor functions of cyclin D1 are distinct. In addition, our data suggest that properties of the cyclin D1 central domain could be exploited to develop novel prostate cancer therapeutics.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:day
13
pubmed:volume
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
431-44
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
A central domain of cyclin D1 mediates nuclear receptor corepressor activity.
pubmed:affiliation
Department of Cell Biology, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0521, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't