Linked Life Data

20478272

Source:http://linkedlifedata.com/resource/pubmed/id/20478272

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2010-7-19
pubmed:abstractText
Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a halogenated aromatic hydrocarbon and environmental contaminant, results in several deleterious effects, including fetal malformation and cancer. These effects are mediated by the aryl hydrocarbon receptor (AhR), a ligand-activated receptor that regulates the expression of genes encoding xenobiotic-metabolizing enzymes. Several reports suggest that AhR function is beyond the adaptive chemical response. In the present study, we analyzed and compared gene expression profiles of C57BL/6N wild-type (WT) and Ahr-null mice. DNA microarray and quantitative RT-PCR analyses revealed changes in the expression of genes involved in the ubiquitin-proteasome system (UPS). UPS has an important role in cellular homeostasis control and dysfunction of this pathway has been implicated in the development of several human pathologies. Protein ubiquitination is a multi-step enzymatic process that regulates the stability, function, and/or localization of the modified proteins. This system is highly regulated post-translationally by covalent modifications. However, little information regarding the transcriptional regulation of the genes encoding ubiquitin (Ub) proteins is available. Therefore, we investigated the role of the AhR in modulation of the UPS and regulation of Ube2l3 transcription, an E2 ubiquitin-conjugating enzyme, as well as the effects on p53 degradation. Our results indicate that AhR inactivation decreases on liver proteasome activity, probably due to a down-regulation on the expression of several proteasome subunits. On the other hand, AhR activation increases Ube2l3 mRNA and protein levels by controlling Ube2l3 gene expression, resulting in increased p53 ubiquitination and degradation. In agreement with this, induction of apoptosis was attenuated by the AhR activation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1873-2968
pubmed:author
pubmed:copyrightInfo
Copyright 2010 Elsevier Inc. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
80
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
932-40
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Ube2l3 gene expression is modulated by activation of the aryl hydrocarbon receptor: implications for p53 ubiquitination.
pubmed:affiliation
Departamento de Toxicología, CINVESTAV-IPN, Zacatenco. México D.F., Av. IPN 2508, C.P. 07360, Mexico.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't