Phosphorylation of NF-kappa B by calmodulin-dependent kinase IV activates anti-apoptotic gene expression.

Department of Molecular Biology, Pusan National University, Pusan 609-735, Republic of Korea.
Biochemical and Biophysical Research Communications (Impact Factor: 2.28). 07/2003; 305(4):1094-8. DOI: 10.1016/S0006-291X(03)00869-6
Source: PubMed

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.

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