Linked Life Data

11971907

Source:http://linkedlifedata.com/resource/pubmed/id/11971907

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
26
pubmed:dateCreated
2002-6-24
pubmed:abstractText
Myotrophin/V-1 is a cytosolic protein found at elevated levels in failing human hearts and in postnatal cerebellum. We have previously shown that it disrupts nuclear factor of kappaB (NFkappaB)-DNA complexes in vitro. In this study, we demonstrated that in HeLa cells native myotrophin/V-1 is predominantly present in the cytoplasm and translocates to the nucleus during sustained NFkappaB activation. Three-dimensional alignment studies indicate that myotrophin/V-1 resembles a truncated IkappaBalpha without the signal response domain (SRD) and PEST domains. Co-immunoprecipitation studies reveal that myotrophin/V-1 interacts with NFkappaB proteins in vitro; however, it remains physically associated only with p65 and c-Rel proteins in vivo during NFkappaB activation. In vitro studies indicate that myotrophin/V-1 can promote the formation of p50-p50 homodimers from monomeric p50 proteins and can convert the preformed p50-p65 heterodimers into p50-p50 and p65-p65 homodimers. Furthermore, adenovirus-mediated overexpression of myotrophin/V-1 resulted in elevated levels of both p50-p50 and p65-p65 homodimers exceeding the levels of p50-p65 heterodimers compared with Adbetagal-infected cells, where the levels of p50-p65 heterodimers exceeded the levels of p50-p50 and p65-p65 homodimers. Thus, overexpression of myotrophin/V-1 during NFkappaB activation resulted in a qualitative shift by quantitatively reducing the level of transactivating heterodimers while elevating the levels of repressive p50-p50 homodimers. Correspondingly, overexpression of myotrophin/V-1 resulted in significantly reduced kappaB-luciferase reporter activity. Because myotrophin/V-1 is found at elevated levels during NFkappaB activation in postnatal cerebellum and in failing human hearts, this study cumulatively suggests that myotrophin/V-1 is a regulatory protein for modulating the levels of activated NFkappaB dimers during this period.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
28
pubmed:volume
277
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
23888-97
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:11971907-Amino Acid Sequence, pubmed-meshheading:11971907-Biological Transport, pubmed-meshheading:11971907-Cell Nucleus, pubmed-meshheading:11971907-Cerebellum, pubmed-meshheading:11971907-Cytoplasm, pubmed-meshheading:11971907-Dimerization, pubmed-meshheading:11971907-Fluorescent Antibody Technique, Indirect, pubmed-meshheading:11971907-Growth Substances, pubmed-meshheading:11971907-HeLa Cells, pubmed-meshheading:11971907-Heart Failure, pubmed-meshheading:11971907-Humans, pubmed-meshheading:11971907-Intercellular Signaling Peptides and Proteins, pubmed-meshheading:11971907-Molecular Chaperones, pubmed-meshheading:11971907-Molecular Sequence Data, pubmed-meshheading:11971907-NF-kappa B, pubmed-meshheading:11971907-NF-kappa B p50 Subunit, pubmed-meshheading:11971907-Transcription, Genetic, pubmed-meshheading:11971907-Transcription Factor RelA, pubmed-meshheading:11971907-Up-Regulation
pubmed:year
2002
pubmed:articleTitle
Myotrophin/V-1, a protein up-regulated in the failing human heart and in postnatal cerebellum, converts NFkappa B p50-p65 heterodimers to p50-p50 and p65-p65 homodimers.
pubmed:affiliation
Winters Center For Heart Failure Research, Molecular Cardiology Unit, Cardiology Section of Department of Medicine, Baylor College of Medicine, Veterans Affairs Medical Center, Houston, Texas 77030, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't