Linked Life Data

21270532

Source:http://linkedlifedata.com/resource/pubmed/id/21270532

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2011-3-16
pubmed:abstractText
The autocrine motility factor receptor or glycoprotein-78 (gp78) and C-terminus of Hsp70-interacting protein (CHIP) are E3-ligases required for ubiquitination of cytochrome P450s of the 3A subfamily (CYP3A) in endoplasmic reticulum-associated degradation (ERAD). The CYP isozyme 3A4 (CYP3A4) is responsible for the metabolism of the majority of xenobiotics including anticancer agents. Much variability in clinical response to chemotherapy is observed and it has been suggested that variability in CYP3A4 expression could be a factor. The study reviewed in this journal club comments on the importance of further characterizing gp78 and CHIP as relevant proteins in ERAD of CYP3A4. This study demonstrated how both gp78 and CHIP play direct roles in reducing CYP3A4 protein content as well as CYP3A4 ubiquitination. Interestingly, when gp78 and CHIP were knocked down by siRNAs directed towards each protein, the stabilized CYP3A4 remained functional. This has implications for drug-drug interactions for agents metabolized by CYP3A4, which can influence drug exposure levels. This is relevant because most anticancer agents have very narrow therapeutic windows, thus even slight changes in CYP3A4 levels could alter the exposure of that drug and result in either insufficient efficacy or toxicity. Future studies must explore genetic variability in the ERAD pathway and identify new factors that influence CYP3A ERAD in order to better characterize how CYP3A variability affects anticancer drug pharmacology.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1555-8576
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
11
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
549-51
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
CHIP and gp78-mediated ubiquitination of CYP3A4: Implications for the pharmacology of anticancer agents.
pubmed:affiliation
National Cancer Institute, Bethesda, MD, USA.
pubmed:publicationType
Journal Article, Review