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MBC in Press, published online ahead of print October 18, 2006
Mol. Biol. Cell 10.1091/mbc.E06-04-0280

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Submitted on April 7, 2006
Revised on September 29, 2006
Accepted on October 5, 2006

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 K. Batra, and Parmender P. Mehta

Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198

Monitoring Editor: Asma Nusrat

The constituent proteins of gap junctions, called connexin (Cx)s, 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 - posttranslationally. In the absence of androgens, a major fraction of Cx32 is degraded presumably by endoplasmic reticulum associated degradation (ERAD), 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.


Address correspondence to: Parmender P. Mehta (pmehta{at}unmc.edu)







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