Linked Life Data

16835221

Source:http://linkedlifedata.com/resource/pubmed/id/16835221

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
36
pubmed:dateCreated
2006-9-4
pubmed:abstractText
The 92-kDa gelatinase (MMP-9) expression is prerequisite for tissue remodeling in physiology and cancer. However, there are few known regulators of MMP-9 expression. Using an expression cloning strategy, we identified transgelin (SM22), a 22-25-kDa actin-binding protein localized to the cell membrane and cytoplasm, as a novel regulator of MMP-9 expression. Overexpression of a SM22 cDNA in HT1080 cells decreased MMP-9 mRNA/protein levels and diminished in vitro invasion of the latter rescued with exogenous MMP-9. Conversely, small interfering RNA-mediated knockdown of SM22 elevated MMP-9 synthesis, and uterus from SM22-null mice showed strong MMP-9 immunoreactivity compared with wild type animals. The ability of SM22 to repress MMP-9 expression required an intact amino terminus calponin homology domain. MMP-9 expression is driven by ERK signaling and SM22 targeted this pathway as evidenced by (a) the transience in MAPK activation and (b) blunted stimulation of the MMP-9 promoter by a constitutively active MEK expression vector. Progressive deletion analysis located the SM22 responsive region of the MMP-9 promoter to the proximal 90-bp region harboring an AP-1 motif subsequently implicated by site-directed mutagenesis. Furthermore, nuclear extract from the SM22 transfectants showed diminished c-Fos binding to this motif and SM22 expression reduced the activity of an AP-1-driven reporter by 75%. Thus, SM22 adds to a short list of repressors of MMP-9 expression, achieving this by reducing AP-1-dependent trans-activation of the gene by way of compromised ERK activation. Diminished transgelin expression in several cancers may thus partly account for the elevated MMP-9 expression evident in these tumors.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
8
pubmed:volume
281
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
26424-36
pubmed:dateRevised
2011-11-10
pubmed:meshHeading
pubmed-meshheading:16835221-Actins, pubmed-meshheading:16835221-Animals, pubmed-meshheading:16835221-Cell Line, pubmed-meshheading:16835221-Enzyme Activation, pubmed-meshheading:16835221-Extracellular Signal-Regulated MAP Kinases, pubmed-meshheading:16835221-Female, pubmed-meshheading:16835221-Fibroblasts, pubmed-meshheading:16835221-Gene Expression Regulation, Enzymologic, pubmed-meshheading:16835221-Humans, pubmed-meshheading:16835221-Lung, pubmed-meshheading:16835221-MAP Kinase Signaling System, pubmed-meshheading:16835221-Matrix Metalloproteinase 9, pubmed-meshheading:16835221-Mice, pubmed-meshheading:16835221-Mice, Knockout, pubmed-meshheading:16835221-Microfilament Proteins, pubmed-meshheading:16835221-Muscle Proteins, pubmed-meshheading:16835221-Mutagenesis, Site-Directed, pubmed-meshheading:16835221-Promoter Regions, Genetic, pubmed-meshheading:16835221-Protein Structure, Tertiary, pubmed-meshheading:16835221-RNA, Small Interfering, pubmed-meshheading:16835221-Transcriptional Activation, pubmed-meshheading:16835221-Uterus
pubmed:year
2006
pubmed:articleTitle
Expression cloning identifies transgelin (SM22) as a novel repressor of 92-kDa type IV collagenase (MMP-9) expression.
pubmed:affiliation
Department of Cancer Biology, M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural