scholarly journals Genetic Deletion of Glycogen Synthase Kinase-3β Abrogates Activation of IκBα Kinase, JNK, Akt, and p44/p42 MAPK but Potentiates Apoptosis Induced by Tumor Necrosis Factor

2004 ◽  
Vol 279 (38) ◽  
pp. 39541-39554 ◽  
Author(s):  
Yasunari Takada ◽  
Xianjun Fang ◽  
Md. Saha Jamaluddin ◽  
Douglas D. Boyd ◽  
Bharat B. Aggarwal
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Glycogen Synthase ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3Β ◽  
Genetic Deletion ◽  
Necrosis Factor

scholarly journals Glycogen Synthase Kinase 3β Functions To Specify Gene-Specific, NF-κB-Dependent Transcription

2005 ◽  
Vol 25 (19) ◽  
pp. 8444-8455 ◽  
Author(s):  
Kris A. Steinbrecher ◽  
Willie Wilson ◽  
Patricia C. Cogswell ◽  
Albert S. Baldwin
Keyword(s):  
Tumor Necrosis Factor ◽  
Interleukin 6 ◽  
Tumor Necrosis ◽  
Glycogen Synthase ◽  
Glycogen Synthase Kinase 3Β ◽  
Monocyte Chemoattractant Protein 1 ◽  
Monocyte Chemoattractant ◽  
Monocyte Chemoattractant Protein ◽  
Gsk 3Β ◽  
Necrosis Factor

ABSTRACT Loss of glycogen synthase kinase 3β (GSK-3β) in mice results in embryonic lethality via hepatocyte apoptosis. Consistent with this result, cells from these mice have diminished nuclear factor κB (NF-κB) activity, implying a functional role for GSK-3β in regulating NF-κB. Here, we have explored mechanisms by which GSK-3β may control NF-κB function. We show that cytokine-induced IκB kinase activity and subsequent phosphorylation of IκBα, p105, and p65 are not affected by the absence of GSK-3β activity. Furthermore, nuclear accumulation of p65 following tumor necrosis factor treatment is unaffected by the loss of GSK-3β. However, NF-κB DNA binding activity is reduced in GSK-3β null cells and in cells treated with a pharmacological inhibitor of GSK-3. Expression of certain NF-κB-regulated genes, such as IκBα and macrophage inflammatory protein 2, is minimally affected by the absence of GSK-3β. Conversely, we have identified a subset of NF-κB-regulated genes, including those for interleukin-6 and monocyte chemoattractant protein 1, that require GSK-3β for efficient expression. We show that efficient localization of p65 to the promoter regions of the interleukin-6 and monocyte chemoattractant protein 1 genes following tumor necrosis factor alpha treatment requires GSK-3β. Therefore, GSK-3β has profound effects on transcription in a gene-specific manner through a mechanism involving control of promoter-specific recruitment of NF-κB.

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