Glycogen synthase kinase-3beta regulates DeltaNp63 gene transcription through the beta-catenin signaling pathway.
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.
Chu
Wing-Keung
WK
Department of Physiology, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan.
Dai
Pei-Min
PM
Li
Hsin-Lun
HL
Chen
Jan-Kan
JK
D002460:Cell Line; D038362:Glycogen Synthase Kinase 3 / Q000502:physiology*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D018021:Lithium Chloride / Q000494:pharmacology; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000502:physiology*; D011401:Promoter Regions, Genetic; D020218:Response Elements; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics*; D014157:Transcription Factors; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D051176:beta Catenin / Q000378:metabolism*
D051821:Lymphoid Enhancer-Binding Factor 1; C115051:TP63 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D051176:beta Catenin; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; D018021:Lithium Chloride