Linked Life Data

18850005

Source:http://linkedlifedata.com/resource/pubmed/id/18850005

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2009-1-22
pubmed:abstractText
Cortactin binds F-actin and promotes cell migration. We showed earlier that cortactin is acetylated. Here, we identify SIRT1 (a class III histone deacetylase) as a cortactin deacetylase and p300 as a cortactin acetylase. We show that SIRT1 deacetylates cortactin in vivo and in vitro and that the SIRT1 inhibitor EX-527 increases amounts of acetylated cortactin in ovarian cancer cells. We also show that p300 acetylates cortactin in vivo and that cells lacking or depleted of p300 express less-acetylated cortactin than do control cells. Deletion analysis mapped the SIRT1-binding domain of cortactin to its repeat region, which also binds F-actin. Mouse embryo fibroblasts (MEFs) lacking sir2alpha (the mouse homolog of SIRT1) migrated more slowly than did wild-type cells. The expression of SIRT1 in sir2alpha-null cells restored migratory capacity, as did expression of a deacetylation-mimetic mutant of cortactin. SIRT1 and cortactin were more abundant in breast tumor tissue than in their normal counterparts, whereas SIRT1 expression inversely correlates with the ratio of acetylation cortactin versus total cortactin. These data suggest that deacetylation of cortactin is associated with high levels of SIRT1 and tumorigenesis. Finally, breast and ovarian cancer cell lines expressing an acetylation mimetic mutant of cortactin are less motile than that of control cells, whereas cells expressing the deacetylation mimetic mutant of cortactin migrate faster than that of control cells in Transwell migration assays. In summary, our results suggest that cortactin is a novel substrate for SIRT1 and p300 and, for the first time, a possible role for SIRT1 in cell motility through deacetylation of cortactin.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1476-5594
pubmed:author
pubmed:issnType
Electronic
pubmed:day
22
pubmed:volume
28
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
445-60
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:18850005-Acetylation, pubmed-meshheading:18850005-Animals, pubmed-meshheading:18850005-Blotting, Western, pubmed-meshheading:18850005-Breast, pubmed-meshheading:18850005-Breast Neoplasms, pubmed-meshheading:18850005-Cell Migration Assays, pubmed-meshheading:18850005-Cell Movement, pubmed-meshheading:18850005-Cell Nucleus, pubmed-meshheading:18850005-Cells, Cultured, pubmed-meshheading:18850005-Cortactin, pubmed-meshheading:18850005-Cytoplasm, pubmed-meshheading:18850005-E1A-Associated p300 Protein, pubmed-meshheading:18850005-Embryo, Mammalian, pubmed-meshheading:18850005-Female, pubmed-meshheading:18850005-Fibroblasts, pubmed-meshheading:18850005-Humans, pubmed-meshheading:18850005-Immunoenzyme Techniques, pubmed-meshheading:18850005-Immunoprecipitation, pubmed-meshheading:18850005-Kidney, pubmed-meshheading:18850005-Mice, pubmed-meshheading:18850005-Ovarian Neoplasms, pubmed-meshheading:18850005-Sirtuin 1, pubmed-meshheading:18850005-Sirtuin 2, pubmed-meshheading:18850005-Sirtuins, pubmed-meshheading:18850005-Wound Healing
pubmed:year
2009
pubmed:articleTitle
Deacetylation of cortactin by SIRT1 promotes cell migration.
pubmed:affiliation
Department of Pathology and Cell Biology, College of Medicine, University of South Florida, Tampa, FL 33612, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't