Plakoglobin deficiency protects keratinocytes from apoptosis

Rachel L. Dusek, Lisa M. Godsel, Feng Chen, Anne M. Strohecker, Spiro Getsios, Robert Harmon, Eliane J. Müller, Reto Caldelari, Vincent L. Cryns, Kathleen J. Green*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

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 β-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-XL 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 β-catenin, to potentiate death in cells damaged by apoptotic stimuli, perhaps limiting the potential for the propagation of mutations and cellular transformation.

Original languageEnglish (US)
Pages (from-to)792-801
Number of pages10
JournalJournal of Investigative Dermatology
Volume127
Issue number4
DOIs
StatePublished - Apr 2007

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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