NDLI: Plakoglobin Regulates the Expression of the Anti-apoptotic Protein BCL-2

Content Provider	Journal of Biological Chemistry (JBC)
Author	Hakimelahi, Shahram Parker, Henry R. Gilchrist, Anita J. Barry, Michele Li, Zhi Bleackley, R. Chris Pasdar, Manijeh
Abstract	Plakoglobin is a cytoplasmic protein and a homologue of β-catenin and Armadillo of Drosophila with similar adhesive and signaling functions. These proteins interact with cadherins to mediate cell-cell adhesion and associate with transcription factors to induce changes in the expression of genes involved in cell fate determination and proliferation. Unlike the relatively well characterized role of β-catenin in cell proliferation via activation of c-MYC and cyclin D1 gene expression, the signaling function of plakoglobin in regulation of cell growth is undefined. Here, we show that high levels of plakoglobin expression in plakoglobin-deficient human SCC9 cells leads to uncontrolled growth and foci formation. Concurrent with the change in growth characteristics we observe a pronounced inhibition of apoptosis. This correlates with an induction of expression of BCL-2, a prototypic member of apoptosis-regulating proteins. TheBCL-2 expression coincides with decreased proteolytic processing and activation of caspase-3, an executor of programmed cell death. Our data suggest that the growth regulatory function of plakoglobin is independent of its role in mediating cell-cell adhesion. These observations clearly implicate plakoglobin in pathways regulating cell growth and provide initial evidence of its role as a pivotal molecular link between pathways regulating cell adherence and cell death.
Related Links	http://www.jbc.org/content/275/15/10905.abstract
Ending Page	10911
Starting Page	10905
Page Count	7
File Format	HTM / HTML PDF
ISSN	00219258
Journal	Journal of Biological Chemistry (JBC)
Issue Number	15
Volume Number	275
DOI	10.1074/jbc.275.15.10905
e-ISSN	1083351X
Language	English
Publisher	American Society for Biochemistry and Molecular Biology
Publisher Date	2000-04-14
Access Restriction	Open
Subject Keyword	Lymphoid enhancer factor/T-cell factor (LEF/TCF) Adenomatous polyposis coli (APC) Terminal transferase-catalyzed dUTP end labeling (TUNEL) 1,4-piperazinediethanesulfonic acid (PIPES) Cytomegalovirus (CMV) MOLECULAR BASIS OF CELL AND DEVELOPMENTAL BIOLOGY
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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