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Titolo:
Importance of the regulation of nuclear receptor degradation
Autore:
Dennis, AP; Haq, RU; Nawaz, Z;
Indirizzi:
Baylor Coll Med, Houston, TX 77030 USA Baylor Coll Med Houston TX USA 77030 ylor Coll Med, Houston, TX 77030 USA
Titolo Testata:
FRONTIERS IN BIOSCIENCE
, volume: 6, anno: 2001,
pagine: D954 - D959
SICI:
1093-9946(200108)6:<D954:IOTRON>2.0.ZU;2-0
Fonte:
ISI
Lingua:
ENG
Soggetto:
PROTEASOME-DEPENDENT DEGRADATION; UBIQUITIN-PROTEIN LIGASE; THYROID-HORMONE RECEPTOR; RNA-POLYMERASE-II; ESTROGEN-RECEPTOR; 26S PROTEASOME; TRANSCRIPTIONAL COACTIVATOR; HISTONE ACETYLTRANSFERASE; MEDIATED DEGRADATION; HUMAN PROGESTERONE;
Keywords:
nuclear hormone receptor; coactivator; transcription; ubiquitin-proteasome pathway; review;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
52
Recensione:
Indirizzi per estratti:
Indirizzo: Nawaz, Z Baylor Coll Med, 1 Baylor Plaza, Houston, TX 77030 USA Baylor Coll Med 1 Baylor Plaza Houston TX USA 77030 TX 77030 USA
Citazione:
A.P. Dennis et al., "Importance of the regulation of nuclear receptor degradation", FRONT BIOSC, 6, 2001, pp. D954-D959

Abstract

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 becausethe number of receptor molecules available to activate transcription woulddecrease over time. One of the obvious reasons for downregulating 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 activity 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 machinery. Understanding the mechanism of nuclear hormone receptor degradation and its relation to transcription may lead to novel insights of therapuetic intervention.

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Documento generato il 15/01/21 alle ore 23:26:39