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Glycogen synthase kinase‐3β regulates ΔNp63 gene transcription through the β‐catenin signaling pathway
Author(s) -
Chu WingKeung,
Dai PeiMin,
Li HsinLun,
Chen JanKan
Publication year - 2008
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.21839
Subject(s) - gsk 3 , hek 293 cells , catenin , transcription (linguistics) , transcription factor , biology , microbiology and biotechnology , promoter , gsk3b , kinase , carcinogenesis , signal transduction , promoter activity , gene , gene expression , wnt signaling pathway , chemistry , biochemistry , philosophy , linguistics
Overexpression of ΔNp63 has been observed in a number of human cancers, suggesting a role for ΔNp63 in carcinogenesis. In the present study, we show that inhibition of glycogen synthase kinase‐3β (GSK‐3β) by lithium chloride (LiCl) elicited a stimulatory effect on ΔNp63 promoter activity in HEK 293T cells. Exposure to LiCl induced ΔNp63 promoter activation as well as ΔNp63 protein expression in the cells. The effect of GSK‐3β on ΔNp63 expression was further confirmed by the use of two highly specific GSK‐3β inhibitors, SB216763 and SB415286. Further study showed the presence of a putative β‐catenin responsive element (β‐catenin‐RE) in the ΔNp63 promoter region, and the stimulation of ΔNp63 promoter activity by GSK‐3β inhibitor is markedly abolished by mutation or deletion of the putative β‐catenin‐RE. Data are also presented to show that β‐catenin acts together with Lef‐1 to influence ΔNp63 promoter activity and protein expression. J. Cell. Biochem. 105: 447–453, 2008. © 2008 Wiley‐Liss, Inc.