Involvement of glycogen synthase kinase-3beta in hydrogen peroxide-induced suppression of Tcf/Lef-dependent transcriptional activity.
Hydrogen peroxide (H(2)O(2)) mediates induction of cytotoxicity in various cell types. GSK-3beta has been found to participate in a number of signaling pathways, including cell proliferation and cell death. In the present study, we show that GSK-3beta is rapidly dephosphorylated and activated in response to H(2)O(2) treatment. H(2)O(2) also dephosphorylates Akt/PKB in a dose- and time-dependent manner. Overexpression of Akt/PKB attenuates H(2)O(2)-induced dephosphorylation of GSK-3beta. Ectopic expression of Dvl-1, a component of Wnt signaling, stimulates Akt/PKB and inhibits dephosphorylation of GSK-3beta by H(2)O(2). Furthermore, H(2)O(2) causes the reduction of beta-catenin level and LiCl-mediated activation of Tcf/Lef-dependent transcription activity. These findings suggest that GSK-3beta is involved in H(2)O(2)-mediated inhibition of Tcf/Lef-dependent transcriptional activity.
Shin
Soon Young
SY
Division of Molecular and Life Science, College of Science and Technology, Hanyang University, Ansan 426-791, Korea.
Chin
Byung Rho
BR
Lee
Young Han
YH
Kim
Jung-Hye
JH
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000072261:Dishevelled Proteins; D004789:Enzyme Activation; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D018021:Lithium Chloride / Q000378:metabolism; D051379:Mice; D041681:NIH 3T3 Cells; D016877:Oxidants / Q000378:metabolism*; D010750:Phosphoproteins; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D051820:TCF Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D048868:Adaptor Proteins, Signal Transducing; C000606578:DVL1 protein, human; D000072261:Dishevelled Proteins; C000606579:Dvl1 protein, mouse; D016877:Oxidants; D010750:Phosphoproteins; D011506:Proteins; D051820:TCF Transcription Factors; D012694:Serine; D006861:Hydrogen Peroxide; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; D018021:Lithium Chloride