Overexpression of Pygopus2 protects HeLa cells from vinblastine-induced apoptosis
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Degejing De
Abstract
Pygopus, a very important component of the Wnt signaling transcriptional complex, has multiple functions in both Wnt-dependent and -independent pathways. Human Pygopus2 (Pygo2) is expressed in many cancers and plays an important role in tumor growth. In the present study, we generated human carcinoma (HeLa) cell lines stably expressing Pygo2, which counteracts vinblastine-induced apoptosis. The anti-apoptotic function was determined by DNA fragmentation, sub-G1 appearance, loss of mitochondrial membrane potential (Δψm) and the activation of caspase-9 and caspase-3. In addition, we found that Pygo2 effectively blocks vinblastine-induced c-Jun and AP-1 activation, maintains the anti-apoptotic protein Bcl-2 in an unphosphorylated state, and thus can render cells resistant to apoptosis. However, Pygo2 does not alter the vinblastine-induced cell cycle changes. Here, we describe an anti-apoptotic activity exerted by Pygo2 through blocking activation of the JNK/AP-1 signaling pathway induced by vinblastine.
©2009 by Walter de Gruyter Berlin New York
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Articles in the same Issue
- Minireview
- Functional genetic mouse models: promising tools for investigation of the proteolytic internet
- Protein Structure and Function
- Primary sequence, together with other factors, influence peptide deimination by peptidylarginine deiminase-4
- Mercury and cadmium trigger expression of the copper importer Ctr1B, which enables Drosophila to thrive on heavy metal-loaded food
- Cell Biology and Signaling
- Interferon-γ-mediated pathways and in vitro PBMC proliferation in HIV-infected patients
- Exploring the pathogenesis of renal cell carcinoma: pathway and bioinformatics analysis of dysregulated genes and proteins
- Aptamers selected against the unglycosylated EGFRvIII ectodomain and delivered intracellularly reduce membrane-bound EGFRvIII and induce apoptosis
- Involvement of heparan sulfate proteoglycans in cellular uptake of high molecular weight kininogen
- Overexpression of Pygopus2 protects HeLa cells from vinblastine-induced apoptosis
- Proteolysis
- Selectivity of propeptide-enzyme interaction in cathepsin L-like cysteine proteases
- Murine and human cathepsin B exhibit similar properties: possible implications for drug discovery
- Novel Techniques
- Isotope tracing enhancement of chemiluminescence assays for nitric oxide research
