Abstract
We previously presented that calmodulin-dependent kinase IV (CaMKIV) mutually interacts with NF-kappa B and phosphorylates it directly, inducing the increased transcriptional regulation dependent on NF-kappa B target genes [J. Biol. Chem. 276 (2001) 20005]. Here, we show that Ser(535) residue is phosphorylated by CaMKIV. S535A mutant of p65 was specifically defective in transactivation of NF-kappa B target gene expression induced by CaMKIV. While coexpression of active CaMKIV with wild-type p65 led to a recovery from etoposide-induced apoptosis and an increase of Bcl-2 protein in cells, cells expressing S535A mutant did not. Taken together these results suggest that phosphorylated NF-kappa B p65 on Ser(535) by CaMKIV increases NF-kappa B target gene expression, including anti-apoptotic gene, hence leading to inhibition of apoptosis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis*
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CREB-Binding Protein
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Calcium-Calmodulin-Dependent Protein Kinase Type 4
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
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DNA-Binding Proteins / metabolism
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HeLa Cells
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Humans
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Mutation
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NF-kappa B / chemistry
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NF-kappa B / genetics
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NF-kappa B / metabolism*
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Nuclear Proteins / metabolism
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Nuclear Receptor Co-Repressor 2
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Phosphorylation
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Repressor Proteins / metabolism
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Serine / metabolism
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Trans-Activators / metabolism
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Transcription Factor RelA
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Transcriptional Activation*
Substances
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DNA-Binding Proteins
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NCOR2 protein, human
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NF-kappa B
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Nuclear Proteins
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Nuclear Receptor Co-Repressor 2
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Repressor Proteins
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Trans-Activators
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Transcription Factor RelA
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Serine
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CREB-Binding Protein
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CREBBP protein, human
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CAMK4 protein, human
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Calcium-Calmodulin-Dependent Protein Kinase Type 4
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Calcium-Calmodulin-Dependent Protein Kinases