Linked Life Data

20724525

Source:http://linkedlifedata.com/resource/pubmed/id/20724525

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2010-12-2
pubmed:abstractText
Growing evidence indicates a critical role of ubiquitin-proteosome system in apoptosis regulation. A cardioprotective effect of ubiquitin (Ub) ligase of the C terminus of Hsc70-interacting protein (CHIP) on myocytes has been reported. In the current study, we found that the cardioprotective effect of insulin growth factor-1 (IGF-1) was mediated by ERK5-CHIP signal module via inducible cAMP early repressor (ICER) destabilization. In vitro runoff assay and Ub assay showed ICER as a substrate of CHIP Ub ligase. Both disruption of ERK5-CHIP binding with inhibitory helical linker domain fragment (aa 101-200) of CHIP and the depletion of ERK5 by siRNA inhibited CHIP Ub ligase activity, which suggests an obligatory role of ERK5 on CHIP activation. Depletion of CHIP, using siRNA, inhibited IGF-1-mediated reduction of isoproterenol-mediated ICER induction and apoptosis. In diabetic mice subjected to myocardial infarction, the CHIP Ub ligase activity was decreased, with an increase in ICER expression. These changes were attenuated significantly in a cardiac-specific constitutively active form of MEK5? transgenic mice (CA-MEK5?-Tg) previously shown to have greater functional recovery. Furthermore, pressure overload-mediated ICER induction was enhanced in heterozygous CHIP(+/-) mice. We identified ICER as a novel CHIP substrate and that the ERK5-CHIP complex plays an obligatory role in inhibition of ICER expression, cardiomyocyte apoptosis, and cardiac dysfunction.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1530-6860
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4917-28
pubmed:dateRevised
2011-8-1
pubmed:meshHeading
pubmed-meshheading:20724525-Animals, pubmed-meshheading:20724525-Animals, Newborn, pubmed-meshheading:20724525-Apoptosis, pubmed-meshheading:20724525-Blotting, Western, pubmed-meshheading:20724525-Cells, Cultured, pubmed-meshheading:20724525-Cyclic AMP, pubmed-meshheading:20724525-Cyclic AMP Response Element Modulator, pubmed-meshheading:20724525-Echocardiography, pubmed-meshheading:20724525-Immunoprecipitation, pubmed-meshheading:20724525-Mitogen-Activated Protein Kinase 7, pubmed-meshheading:20724525-Myocytes, Cardiac, pubmed-meshheading:20724525-Protein Binding, pubmed-meshheading:20724525-Protein Stability, pubmed-meshheading:20724525-RNA, Small Interfering, pubmed-meshheading:20724525-Rats, pubmed-meshheading:20724525-Rats, Sprague-Dawley, pubmed-meshheading:20724525-Ubiquitin-Protein Ligases
pubmed:year
2010
pubmed:articleTitle
Novel role of C terminus of Hsc70-interacting protein (CHIP) ubiquitin ligase on inhibiting cardiac apoptosis and dysfunction via regulating ERK5-mediated degradation of inducible cAMP early repressor.
pubmed:affiliation
Aab Cardiovascular Research Institute, University of Rochester, Rochester, New York 14642, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural