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Title: HepaCAM associates with connexin 43 and enhances its localization in cellular junctions
Authors: Wu M. 
Moh M.C. 
Schwarz H. 
Keywords: connexin 43
HEPACAM protein, human
tumor suppressor protein
gap junction
tumor cell line
Cell Line, Tumor
Connexin 43
Gap Junctions
Tumor Suppressor Proteins
Issue Date: 2016
Publisher: Nature Publishing Group
Citation: Wu M., Moh M.C., Schwarz H. (2016). HepaCAM associates with connexin 43 and enhances its localization in cellular junctions. Scientific Reports 6 : 36218. ScholarBank@NUS Repository.
Abstract: HepaCAM (GlialCAM) is frequently deleted in carcinomas, and reintroduction of hepaCAM into transformed cell lines reduces cellular growth and induces senescence. Mutations in HEPACAM give rise to the neurodegenerative disease megalencephalic leukoencephalopathy with subcortical cysts (MLC) since mutated hepaCAM prevents shuttling of MLC1 protein to astrocytic junctions in the plasma membrane. Here we identify that hepaCAM associates with connexin 43, a main component of gap junctions, and enhances connexin 43 localization to the plasma membrane at cellular junctions. HepaCAM also increases the levels of connexin 43, not by enhancing its transcription but by stabilizing connexin 43 protein. In the absence of hepaCAM, connexin 43 undergoes a faster degradation via the lysosomal pathway while proteasomal degradation seems not to be involved. Mutations in hepaCAM that cause MLC, or neutralization of hepaCAM by antibodies disrupt its association with connexin 43 at cellular junctions. By discovering the requirement of hepaCAM for localizing connexin 43, a well-established tumor suppressor, to cellular junctions and stabilizing it there, this study suggests a mechanism by which deletion of hepaCAM may support tumor progression. © The Author(s) 2016.
Source Title: Scientific Reports
ISSN: 20452322
DOI: 10.1038/srep36218
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