Linked Life Data

18635971

Source:http://linkedlifedata.com/resource/pubmed/id/18635971

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
14
pubmed:dateCreated
2008-7-25
pubmed:abstractText
Fatty Acid Synthase (FASN), a cytoplasmic biosynthetic enzyme, is the major source of long-chain fatty acids, particularly palmitate. Caveolin-1 (Cav-1) is a palmitoylated lipid raft protein that plays a key role in signal transduction and cholesterol transport. Both proteins have been implicated in prostate cancer (PCa) progression, and Cav-1 regulates FASN expression in a mouse model of aggressive PCa. We demonstrate that FASN and Cav-1 are coordinately upregulated in human prostate tumors in a hormone-insensitive manner. Levels of FASN and Cav-1 protein expression discriminated between localized and metastatic cancers, and the two proteins exhibited analogous subcellular locations in a tumor subset. Endogenous FASN and Cav-1 were reciprocally co-immunoprecipitated from human and murine PCa cells, indicating that FASN forms a complex with Cav-1. FASN, a cytoplasmic enzyme, was induced to associate transiently with lipid raft membranes following alterations in signal transduction within the Src, Akt and EGFR pathways, suggesting that co-localization of FASN and Cav-1 is dependent on activation of upstream signaling mediators. A Cav-1 palmitoylation mutant, Cav-1(C133/143/156S), that prevents phosphorylation by Src, did not interact with FASN. When overexpressed in Cav-1-negative PCa cells, Cav-1(C133/143/156S) caused a reduction of both Src and Akt levels, as well as of their active, phosphorylated forms, in comparison with wild type Cav-1. These findings suggest that FASN and Cav-1 physically and functionally interact in PCa cells. They also imply that palmitoylation within this complex is involved in tumor growth and survival.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1551-4005
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
7
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2257-67
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:18635971-Animals, pubmed-meshheading:18635971-Caveolin 1, pubmed-meshheading:18635971-Cell Line, Tumor, pubmed-meshheading:18635971-Enzyme Activation, pubmed-meshheading:18635971-Fatty Acid Synthetase Complex, pubmed-meshheading:18635971-Humans, pubmed-meshheading:18635971-Male, pubmed-meshheading:18635971-Membrane Microdomains, pubmed-meshheading:18635971-Mice, pubmed-meshheading:18635971-Mutation, pubmed-meshheading:18635971-Palmitic Acid, pubmed-meshheading:18635971-Phosphatidylinositol 3-Kinases, pubmed-meshheading:18635971-Prostate, pubmed-meshheading:18635971-Prostatic Neoplasms, pubmed-meshheading:18635971-Protein Binding, pubmed-meshheading:18635971-Protein Kinase Inhibitors, pubmed-meshheading:18635971-Protein Transport, pubmed-meshheading:18635971-Proto-Oncogene Proteins pp60(c-src), pubmed-meshheading:18635971-Signal Transduction
pubmed:year
2008
pubmed:articleTitle
Caveolin-1 interacts with a lipid raft-associated population of fatty acid synthase.
pubmed:affiliation
The Urological Diseases Research Center and Department of Surgery, Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts 02115, USA. dolores.divizio@childrens.harvard.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural