Plakoglobin Deficiency Protects Keratinocytes from Apoptosis.
From: Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.
The Journal of investigative dermatology
- Publish Date: Apr 2007
- ISSN: 1523-1747
- Volume: 127
- Issue: 4
- Pages: 792-801
- Medium: Internet
- Language: English
- Citation (JAMA): Dusek Rachel L, Godsel Lisa M, Chen Feng, et al. Plakoglobin Deficiency Protects Keratinocytes from Apoptosis.. J. Invest. Dermatol. Apr 2007;127:792-801
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 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.
Mesh Headings (Keywords): Animals, Apoptosis, Caspase 3, Cell Proliferation, Cells, Cultured, Cytochromes c, Enzyme Activation, Keratinocytes, Mice, Mice, Knockout, Mitochondria, RNA, Messenger, Time Factors, bcl-X Protein, gamma Catenin
Check for Full Text / PubMed Unique Identifier (PMID): 17110936
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.