Glycogen synthase kinase-3beta regulates DeltaNp63 gene transcription through the beta-catenin signaling pathway

J Cell Biochem. 2008 Oct 1;105(2):447-53. doi: 10.1002/jcb.21839.

Abstract

Overexpression of DeltaNp63 has been observed in a number of human cancers, suggesting a role for DeltaNp63 in carcinogenesis. In the present study, we show that inhibition of glycogen synthase kinase-3beta (GSK-3beta) by lithium chloride (LiCl) elicited a stimulatory effect on DeltaNp63 promoter activity in HEK 293T cells. Exposure to LiCl induced DeltaNp63 promoter activation as well as DeltaNp63 protein expression in the cells. The effect of GSK-3beta on DeltaNp63 expression was further confirmed by the use of two highly specific GSK-3beta inhibitors, SB216763 and SB415286. Further study showed the presence of a putative beta-catenin responsive element (beta-catenin-RE) in the DeltaNp63 promoter region, and the stimulation of DeltaNp63 promoter activity by GSK-3beta inhibitor is markedly abolished by mutation or deletion of the putative beta-catenin-RE. Data are also presented to show that beta-catenin acts together with Lef-1 to influence DeltaNp63 promoter activity and protein expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Glycogen Synthase Kinase 3 / physiology*
  • Glycogen Synthase Kinase 3 beta
  • Humans
  • Lithium Chloride / pharmacology
  • Lymphoid Enhancer-Binding Factor 1 / physiology*
  • Promoter Regions, Genetic
  • Response Elements
  • Signal Transduction*
  • Trans-Activators / genetics*
  • Transcription Factors
  • Transcription, Genetic*
  • Transcriptional Activation
  • Tumor Suppressor Proteins / genetics*
  • beta Catenin / metabolism*

Substances

  • Lymphoid Enhancer-Binding Factor 1
  • TP63 protein, human
  • Trans-Activators
  • Transcription Factors
  • Tumor Suppressor Proteins
  • beta Catenin
  • GSK3B protein, human
  • Glycogen Synthase Kinase 3 beta
  • Glycogen Synthase Kinase 3
  • Lithium Chloride