Prolonged Protein Turnover of Glyceraldehyde-3-Phosphate Dehydrogenase by Phospholipase C-gamma 1 is Critical for Anchorage-Independent Growth and ATP Synthesis in Transformed Cells

Abstract

Overexpression of phospholipase C-γl (PLC-γl) in rat 3Y1 fibroblasts leads to the formation of tumors in nude mice. However, the molecular mechanism for PLC-γl-mediated cellular transformation has not been studied in detail. In this study, we found that glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a glycolytic enzyme, protein levels were increased substantially in cells overexpressing PLC-γl, and that PLC-γl upregulation of GAPDH was due to a decrease in ubiquitination, followed by sustained protein turnover and subsequent accumulation. These observations suggest that regulation of the turnover rate of GAPDH is critical for anchorage-independent growth and ATP synthesis of transformed cells.

Keywords: :

• Molecular biology
• Signal transduction
• Tumor biology
• Tumor cell biology

ACKNOWLEDGEMENTS

This work was supported by the Daejin University Research Grants in 2008. This work has not been published elsewhere and that it has not been submitted simultaneously for publication elsewhere.