Signal transducer and activator of transcription 6 (STAT6) Is a novel interactor of annexin A2 in prostate cancer cells

Susobhan Das, Praveenkumar Shetty, Mallika Valapala, Subhamoy Dasgupta, Zygmunt Gryczynski, Jamboor K. Vishwanatha

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Annexin A2 (AnxA2) is a multifunctional Ca2+-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 twohybrid 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.

Original languageEnglish
Pages (from-to)2216-2226
Number of pages11
JournalBiochemistry
Volume49
Issue number10
DOIs
StatePublished - 16 Mar 2010

Fingerprint

STAT6 Transcription Factor
Annexin A2
Annexins
Prostatic Neoplasms
Cells
Assays
Prostate
STAT Transcription Factors
Neoplasms
Fluorescence Resonance Energy Transfer
Chromatin Immunoprecipitation

Cite this

Das, Susobhan ; Shetty, Praveenkumar ; Valapala, Mallika ; Dasgupta, Subhamoy ; Gryczynski, Zygmunt ; Vishwanatha, Jamboor K. / Signal transducer and activator of transcription 6 (STAT6) Is a novel interactor of annexin A2 in prostate cancer cells. In: Biochemistry. 2010 ; Vol. 49, No. 10. pp. 2216-2226.
@article{d243d24c2c40406187d64389ab3f242e,
title = "Signal transducer and activator of transcription 6 (STAT6) Is a novel interactor of annexin A2 in prostate cancer cells",
abstract = "Annexin A2 (AnxA2) is a multifunctional Ca2+-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 twohybrid 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.",
author = "Susobhan Das and Praveenkumar Shetty and Mallika Valapala and Subhamoy Dasgupta and Zygmunt Gryczynski and Vishwanatha, {Jamboor K.}",
year = "2010",
month = "3",
day = "16",
doi = "10.1021/bi9013038",
language = "English",
volume = "49",
pages = "2216--2226",
journal = "Biochemistry",
issn = "0006-2960",
publisher = "American Chemical Society",
number = "10",

}

Signal transducer and activator of transcription 6 (STAT6) Is a novel interactor of annexin A2 in prostate cancer cells. / Das, Susobhan; Shetty, Praveenkumar; Valapala, Mallika; Dasgupta, Subhamoy; Gryczynski, Zygmunt; Vishwanatha, Jamboor K.

In: Biochemistry, Vol. 49, No. 10, 16.03.2010, p. 2216-2226.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Signal transducer and activator of transcription 6 (STAT6) Is a novel interactor of annexin A2 in prostate cancer cells

AU - Das, Susobhan

AU - Shetty, Praveenkumar

AU - Valapala, Mallika

AU - Dasgupta, Subhamoy

AU - Gryczynski, Zygmunt

AU - Vishwanatha, Jamboor K.

PY - 2010/3/16

Y1 - 2010/3/16

N2 - Annexin A2 (AnxA2) is a multifunctional Ca2+-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 twohybrid 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.

AB - Annexin A2 (AnxA2) is a multifunctional Ca2+-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 twohybrid 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.

UR - http://www.scopus.com/inward/record.url?scp=77949373693&partnerID=8YFLogxK

U2 - 10.1021/bi9013038

DO - 10.1021/bi9013038

M3 - Article

C2 - 20121258

AN - SCOPUS:77949373693

VL - 49

SP - 2216

EP - 2226

JO - Biochemistry

JF - Biochemistry

SN - 0006-2960

IS - 10

ER -