Overload of the heat-shock protein H11/HspB8 triggers melanoma cell apoptosis through activation of transforming growth factor-β-activated kinase 1
Open Access
- 18 December 2006
- journal article
- research article
- Published by Springer Science and Business Media LLC in Oncogene
- Vol. 26 (24), 3521-3531
- https://doi.org/10.1038/sj.onc.1210145
Abstract
Molecular therapeutics is a recognized promising approach for melanoma, but relevant target genes remain elusive. We report that overload of the recently cloned H11/HspB8 induces apoptosis in 55% of examined melanoma cultures. Apoptosis was determined by activation of caspases-9 and -3 and terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL), and was not seen in normal melanocytes. It was associated with H11/HspB8 complexation with transforming growth factor-β-activated kinase (TAK) 1 and activation of TAK1 and p38 mitogen activated protein 3 kinases. TAK1 was not bound, nor activated by the H11/HspB8 mutant W51C, which has dominant antiapoptotic activity. β-Catenin was phosphorylated by activated TAK1, inhibiting its nuclear accumulation and mictophthalmia-associated transcription factor and cyclin dependent kinase 2 expression. The dominant-negative TAK1 mutant K63W inhibited β-catenin phosphorylation and caspase activation. The data indicate that H11/HspB8 overload causes melanoma growth arrest and apoptosis through TAK1 activation and suggest that H11/HspB8 is a promising molecular therapy target.This publication has 37 references indexed in Scilit:
- Aberrant DNA Methylation Silences the Novel Heat Shock Protein H11 in Melanoma but Not Benign Melanocytic LesionsDermatology, 2006
- Paclitaxel (Taxol) upregulates expression of functional interleukin-6 in human ovarian cancer cells through multiple signaling pathwaysOncogene, 2006
- H11 has dose-dependent and dual hypertrophic and proapoptotic functions in cardiac myocytesBiochemical Journal, 2005
- Critical Roles of Threonine 187 Phosphorylation in Cellular Stress-induced Rapid and Transient Activation of Transforming Growth Factor-β-activated Kinase 1 (TAK1) in a Signaling Complex Containing TAK1-binding Protein TAB1 and TAB2Online Journal of Public Health Informatics, 2005
- Mammalian Hsp22 is a heat-inducible small heat-shock protein with chaperone-like activityBiochemical Journal, 2004
- Cdk2-dependent phosphorylation of the NF-Y transcription factor is essential for the expression of the cell cycle-regulatory genes and cell cycle G1/S and G2/M transitionsOncogene, 2004
- Forced Expression of the H11 Heat Shock Protein Can Be Regulated by DNA Methylation and Trigger Apoptosis in Human CellsOnline Journal of Public Health Informatics, 2003
- Expression profiling reveals that methylation of TIMP3 is involved in uveal melanoma developmentInternational Journal of Cancer, 2003
- Microphthalmia-Associated Transcription Factor in the Wnt Signaling PathwayPigment Cell Research, 2003
- TGF-β signaling: positive and negative effects on tumorigenesisCurrent Opinion in Genetics & Development, 2002