Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2001-8-6
pubmed:abstractText
Nuclear hormone receptors (NHRs) represent a superfamily of structurally related ligand-activated transcription factors, which regulate diverse biological activities like growth, development, and homeostasis. Recently, it has been demonstrated that certain members of the NHR superfamily are degraded through the ubiquitin-proteasome pathway in a ligand-dependent manner. Though the signal for the down-regulation via the ubiquitin-proteasome pathway is not yet known, phosphorylation at specific amino acid residues or coactivator binding to receptors could lead to their degradation by the 26S proteasome. Activation and degradation seems to be an engineered cyclic mechanism, which provides tight control over diverse cellular processes. The degradation process involves extensive loss of proteins and requires expenditure of cellular ATP. That seems to be inevitable for a more important aim, that is efficient and appropriate regulation of transcription. Down-regulation of receptors would lead to an attenuated transcriptional response because the number of receptor molecules available to activate transcription would decrease over time. One of the obvious reasons for down-regulating NHRs thus seems to be to prevent the cell from overstimulation by the hormones or other activating signals. Nuclear receptor turnover may also reset the transcriptional apparatus in preparation for a subsequent response. Since inhibition of the ubiquitin-proteasome degradation pathway disturbs the transcriptional activitity of some of the nuclear receptors such as estrogen (ER) and progesterone (PR) receptors, it is also possible that the degradation of NHRs may enable recycling of components of receptor-cofactor complexes and general transcriptional machinary. Understanding the mechanism of nuclear hormone receptor degradation and its relation to transcription may lead to novel insights of therapuetic intervention.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1093-4715
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
6
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
D954-9
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Importance of the regulation of nuclear receptor degradation.
pubmed:affiliation
Baylor College of Medicine, Houston, TX 77030, USA.
pubmed:publicationType
Journal Article, Review