Plakoglobin deficiency protects keratinocytes from apoptosis

Dusek, Rachel L; Godsel, Lisa M; Chen, Feng; Strohecker, Anne M; Getsios, Spiro; Harmon, Robert; Müller, Eliane J; Caldelari, Reto; Cryns, Vincent L; Green, Kathleen J (2007). Plakoglobin deficiency protects keratinocytes from apoptosis. Journal of Investigative Dermatology, 127(4), pp. 792-801. New York, N.Y.: Nature Publishing 10.1038/sj.jid.5700615

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The armadillo family protein plakoglobin (Pg) is a well-characterized component of anchoring junctions, where it functions to mediate cell-cell adhesion and maintain epithelial tissue integrity. Although its closest homolog beta-catenin acts in the Wnt signaling pathway to dictate cell fate and promote proliferation and survival, the role of Pg in these processes is not well understood. Here, we investigate how Pg affects the survival of mouse keratinocytes by challenging both Pg-null cells and their heterozygote counterparts with apoptotic stimuli. Our results indicate that Pg deletion protects keratinocytes from apoptosis, with null cells exhibiting delayed mitochondrial cytochrome c release and activation of caspase-3. Pg-null keratinocytes also exhibit increased messenger RNA and protein levels of the anti-apoptotic molecule Bcl-X(L) compared to heterozygote controls. Importantly, reintroduction of Pg into the null cells shifts their phenotype towards that of the Pg+/- keratinocytes, providing further evidence that Pg plays a direct role in regulating cell survival. Taken together, our results suggest that in addition to its adhesive role in epithelia, Pg may also function in contrast to the pro-survival tendencies of beta-catenin, to potentiate death in cells damaged by apoptotic stimuli, perhaps limiting the potential for the propagation of mutations and cellular transformation.Journal of Investigative Dermatology advance online publication, 16 November 2006; doi:10.1038/sj.jid.5700615.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Animal Pathology

UniBE Contributor:

Müller, Eliane Jasmine

ISSN:

0022-202X

Publisher:

Nature Publishing

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:45

Last Modified:

04 Apr 2014 21:50

Publisher DOI:

10.1038/sj.jid.5700615

PubMed ID:

17110936

Web of Science ID:

000245314600010

URI:

https://boris.unibe.ch/id/eprint/18687 (FactScience: 894)

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