Androgen-regulated formation and degradation of gap junctions in androgen-responsive human prostate cancer cells

Shalini Mitra, Lakshmanan Annamalai, Souvik Chakraborty, Kristen Johnson, Xiao Hong Song, Surinder Kumar Batra, Parmender P Mehta

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

The constituent proteins of gap junctions, called connexins (Cxs), have a short half-life. Despite this, the physiological stimuli that control the assembly of Cxs into gap junctions and their degradation have remained poorly understood. We show here that in androgen-responsive human prostate cancer cells, androgens control the expression level of Cx32-and hence the extent of gap junction formation-post-translationally. In the absence of androgens, a major fraction of Cx32 is degraded presumably by endoplasmic reticulum-associated degradation, whereas in their presence, this fraction is rescued from degradation. We also show that Cx32 and Cx43 degrade by a similar mechanism. Thus, androgens regulate the formation and degradation of gap junctions by rerouting the pool of Cxs, which normally would have been degraded from the early secretory compartment, to the cell surface, and enhancing assembly into gap junctions. Androgens had no significant effect on the formation and degradation of adherens and tight junction-associated proteins. The findings that in a cell culture model that mimics the progression of human prostate cancer, degradation of Cxs, as well as formation of gap junctions, are androgen-dependent strongly implicate an important role of junctional communication in the prostate morphogenesis and oncogenesis.

Original languageEnglish (US)
Pages (from-to)5400-5416
Number of pages17
JournalMolecular biology of the cell
Volume17
Issue number12
DOIs
StatePublished - Dec 1 2006

Fingerprint

Gap Junctions
Connexins
Androgens
Prostatic Neoplasms
Endoplasmic Reticulum-Associated Degradation
Tight Junction Proteins
Adherens Junctions
Connexin 43
Morphogenesis
Half-Life
Prostate
Carcinogenesis
Cell Culture Techniques
Communication

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Androgen-regulated formation and degradation of gap junctions in androgen-responsive human prostate cancer cells. / Mitra, Shalini; Annamalai, Lakshmanan; Chakraborty, Souvik; Johnson, Kristen; Song, Xiao Hong; Batra, Surinder Kumar; Mehta, Parmender P.

In: Molecular biology of the cell, Vol. 17, No. 12, 01.12.2006, p. 5400-5416.

Research output: Contribution to journalArticle

Mitra, Shalini ; Annamalai, Lakshmanan ; Chakraborty, Souvik ; Johnson, Kristen ; Song, Xiao Hong ; Batra, Surinder Kumar ; Mehta, Parmender P. / Androgen-regulated formation and degradation of gap junctions in androgen-responsive human prostate cancer cells. In: Molecular biology of the cell. 2006 ; Vol. 17, No. 12. pp. 5400-5416.
@article{acc7836057b341e4b7e0d1719bb3761f,
title = "Androgen-regulated formation and degradation of gap junctions in androgen-responsive human prostate cancer cells",
abstract = "The constituent proteins of gap junctions, called connexins (Cxs), have a short half-life. Despite this, the physiological stimuli that control the assembly of Cxs into gap junctions and their degradation have remained poorly understood. We show here that in androgen-responsive human prostate cancer cells, androgens control the expression level of Cx32-and hence the extent of gap junction formation-post-translationally. In the absence of androgens, a major fraction of Cx32 is degraded presumably by endoplasmic reticulum-associated degradation, whereas in their presence, this fraction is rescued from degradation. We also show that Cx32 and Cx43 degrade by a similar mechanism. Thus, androgens regulate the formation and degradation of gap junctions by rerouting the pool of Cxs, which normally would have been degraded from the early secretory compartment, to the cell surface, and enhancing assembly into gap junctions. Androgens had no significant effect on the formation and degradation of adherens and tight junction-associated proteins. The findings that in a cell culture model that mimics the progression of human prostate cancer, degradation of Cxs, as well as formation of gap junctions, are androgen-dependent strongly implicate an important role of junctional communication in the prostate morphogenesis and oncogenesis.",
author = "Shalini Mitra and Lakshmanan Annamalai and Souvik Chakraborty and Kristen Johnson and Song, {Xiao Hong} and Batra, {Surinder Kumar} and Mehta, {Parmender P}",
year = "2006",
month = "12",
day = "1",
doi = "10.1091/mbc.E06-04-0280",
language = "English (US)",
volume = "17",
pages = "5400--5416",
journal = "Molecular Biology of the Cell",
issn = "1059-1524",
publisher = "American Society for Cell Biology",
number = "12",

}

TY - JOUR

T1 - Androgen-regulated formation and degradation of gap junctions in androgen-responsive human prostate cancer cells

AU - Mitra, Shalini

AU - Annamalai, Lakshmanan

AU - Chakraborty, Souvik

AU - Johnson, Kristen

AU - Song, Xiao Hong

AU - Batra, Surinder Kumar

AU - Mehta, Parmender P

PY - 2006/12/1

Y1 - 2006/12/1

N2 - The constituent proteins of gap junctions, called connexins (Cxs), have a short half-life. Despite this, the physiological stimuli that control the assembly of Cxs into gap junctions and their degradation have remained poorly understood. We show here that in androgen-responsive human prostate cancer cells, androgens control the expression level of Cx32-and hence the extent of gap junction formation-post-translationally. In the absence of androgens, a major fraction of Cx32 is degraded presumably by endoplasmic reticulum-associated degradation, whereas in their presence, this fraction is rescued from degradation. We also show that Cx32 and Cx43 degrade by a similar mechanism. Thus, androgens regulate the formation and degradation of gap junctions by rerouting the pool of Cxs, which normally would have been degraded from the early secretory compartment, to the cell surface, and enhancing assembly into gap junctions. Androgens had no significant effect on the formation and degradation of adherens and tight junction-associated proteins. The findings that in a cell culture model that mimics the progression of human prostate cancer, degradation of Cxs, as well as formation of gap junctions, are androgen-dependent strongly implicate an important role of junctional communication in the prostate morphogenesis and oncogenesis.

AB - The constituent proteins of gap junctions, called connexins (Cxs), have a short half-life. Despite this, the physiological stimuli that control the assembly of Cxs into gap junctions and their degradation have remained poorly understood. We show here that in androgen-responsive human prostate cancer cells, androgens control the expression level of Cx32-and hence the extent of gap junction formation-post-translationally. In the absence of androgens, a major fraction of Cx32 is degraded presumably by endoplasmic reticulum-associated degradation, whereas in their presence, this fraction is rescued from degradation. We also show that Cx32 and Cx43 degrade by a similar mechanism. Thus, androgens regulate the formation and degradation of gap junctions by rerouting the pool of Cxs, which normally would have been degraded from the early secretory compartment, to the cell surface, and enhancing assembly into gap junctions. Androgens had no significant effect on the formation and degradation of adherens and tight junction-associated proteins. The findings that in a cell culture model that mimics the progression of human prostate cancer, degradation of Cxs, as well as formation of gap junctions, are androgen-dependent strongly implicate an important role of junctional communication in the prostate morphogenesis and oncogenesis.

UR - http://www.scopus.com/inward/record.url?scp=33845391313&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33845391313&partnerID=8YFLogxK

U2 - 10.1091/mbc.E06-04-0280

DO - 10.1091/mbc.E06-04-0280

M3 - Article

C2 - 17050739

AN - SCOPUS:33845391313

VL - 17

SP - 5400

EP - 5416

JO - Molecular Biology of the Cell

JF - Molecular Biology of the Cell

SN - 1059-1524

IS - 12

ER -