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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2010-3-10
pubmed:abstractText
Annexin A2 (AnxA2) is a multifunctional Ca(2+)-dependent phospholipid-binding protein, and its overexpression is implicated in malignant transformation of several cancers. In prostate cancer, however, the expression of AnxA2 is lost in prostate intraepithelial neoplasia and reappears in the high-grade tumors, suggesting a complex regulation of AnxA2 in the prostate microenvironment. Since a majority of the biological functions of AnxA2 are mediated by its interaction with other proteins, we performed a yeast two-hybrid assay to search for novel interactors of AnxA2. Our studies revealed that signal transducer and activator of transcription 6 (STAT6), a member of the STAT family of transcription factors, is a binding partner of AnxA2. We confirmed AnxA2-STAT6 interaction by in vitro co-immunoprecipitation and fluorescence resonance energy transfer (FRET) studies and demonstrated that AnxA2 interacts with phosphorylated STAT6. Furthermore, chromatin immunoprecipitation (ChIP) assay revealed that AnxA2 is associated with the STAT6 DNA-binding complex, and luciferase reporter assays demonstrated that AnxA2 upregulates the activity of STAT6. Upon interleukin-4 treatment, AnxA2 stabilizes the cytosolic levels of phosphorylated STAT6 and promotes its nuclear entry. These findings suggest that AnxA2-STAT6 interactions could have potential implications in prostate cancer progression. This report is the first to demonstrate the interaction of AnxA2 with STAT6 and suggests a possible mechanism by which AnxA2 contributes to the metastatic processes of prostate cancer.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1520-4995
pubmed:author
pubmed:issnType
Electronic
pubmed:day
16
pubmed:volume
49
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2216-26
pubmed:meshHeading
pubmed-meshheading:20121258-Animals, pubmed-meshheading:20121258-Annexin A2, pubmed-meshheading:20121258-Cell Line, Tumor, pubmed-meshheading:20121258-Chromatin Immunoprecipitation, pubmed-meshheading:20121258-DNA, pubmed-meshheading:20121258-Disease Progression, pubmed-meshheading:20121258-Down-Regulation, pubmed-meshheading:20121258-Humans, pubmed-meshheading:20121258-Interleukin-4, pubmed-meshheading:20121258-Male, pubmed-meshheading:20121258-Microscopy, Fluorescence, pubmed-meshheading:20121258-Phosphorylation, pubmed-meshheading:20121258-Prostatic Neoplasms, pubmed-meshheading:20121258-Protein Binding, pubmed-meshheading:20121258-RNA, Small Interfering, pubmed-meshheading:20121258-STAT6 Transcription Factor, pubmed-meshheading:20121258-Transcription, Genetic, pubmed-meshheading:20121258-Two-Hybrid System Techniques
pubmed:year
2010
pubmed:articleTitle
Signal transducer and activator of transcription 6 (STAT6) is a novel interactor of annexin A2 in prostate cancer cells.
pubmed:affiliation
Department of Molecular Biology and Immunology and Institute for Cancer Research, University of North Texas Health Science Center, Fort Worth, Texas 76107, USA.
pubmed:publicationType
Journal Article