Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
16
pubmed:dateCreated
2007-9-21
pubmed:abstractText
RhoA is a crucial regulator of stress fiber and focal adhesion formation through the activation of actin nucleation and polymerization. It also regulates the nuclear translocation of myocardin-related transcription factor-A and -B (MRTF-A/B, MAL or MKL 1/2), which are co-activators of serum response factor (SRF). In dominant-negative MRTF-A (DN-MRTF-A)-expressing NIH 3T3 cell lines, the expressions of several cytoskeletal/focal adhesion genes were down-regulated, and the formation of stress fiber and focal adhesion was severely diminished. MRTF-A/B-knockdown cells also exhibited such cytoskeletal defects. In reporter assays, both RhoA and MRTF-A enhanced promoter activities of these genes in a CArG-box-dependent manner, and DN-MRTF-A inhibited the RhoA-mediated activation of these promoters. In dominant-negative RhoA (RhoA-N19)-expressing NIH 3T3 cell lines, the nuclear translocation of MRTF-A/B was predominantly prevented, resulting in the reduced expression of cytoskeletal/focal adhesion proteins. Further, constitutive-active MRTF-A/B increased the expression of endogenous cytoskeletal/focal adhesion proteins, and thereby rescued the defective phenotype of stress fibers and focal adhesions in RhoA-N19 expressing cells. These results indicate that MRTF-A/B act as pivotal mediators of stress fiber and focal adhesion formation via the transcriptional regulation of a subset of cytoskeletal/focal adhesion genes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0014-4827
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
313
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3432-45
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:17714703-Actins, pubmed-meshheading:17714703-Animals, pubmed-meshheading:17714703-Cytoskeleton, pubmed-meshheading:17714703-Focal Adhesions, pubmed-meshheading:17714703-Gene Expression Regulation, pubmed-meshheading:17714703-Genes, Dominant, pubmed-meshheading:17714703-Humans, pubmed-meshheading:17714703-Mice, pubmed-meshheading:17714703-NIH 3T3 Cells, pubmed-meshheading:17714703-Phenotype, pubmed-meshheading:17714703-Promoter Regions, Genetic, pubmed-meshheading:17714703-Protein Transport, pubmed-meshheading:17714703-Serum Response Factor, pubmed-meshheading:17714703-Stress Fibers, pubmed-meshheading:17714703-Subcellular Fractions, pubmed-meshheading:17714703-Trans-Activators, pubmed-meshheading:17714703-Transcription, Genetic, pubmed-meshheading:17714703-Transcription Factors, pubmed-meshheading:17714703-rhoA GTP-Binding Protein
pubmed:year
2007
pubmed:articleTitle
Reorganization of the actin cytoskeleton via transcriptional regulation of cytoskeletal/focal adhesion genes by myocardin-related transcription factors (MRTFs/MAL/MKLs).
pubmed:affiliation
Depertment of Neuroscience (D13), Osaka University Graduate School of Medicine, Yamadaoka 2-2, Suita, Osaka, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't