Phosphorylation of NF-kappa B by calmodulin-dependent kinase IV activates anti-apoptotic gene expression.
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.
Bae
Jeum Soon
JS
Department of Molecular Biology, Pusan National University, Pusan 609-735, Republic of Korea.
Jang
Moon Kyoo
MK
Hong
SunHwa
S
An
Won Gun
WG
Choi
Yung Hyun
YH
Kim
Han Do
HD
Cheong
JaeHun
J
D017209:Apoptosis; D050882:CREB-Binding Protein; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D009154:Mutation; D016328:NF-kappa B / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D056985:Nuclear Receptor Co-Repressor 2; D010766:Phosphorylation; D012097:Repressor Proteins / Q000378:metabolism; D012694:Serine / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D051996:Transcription Factor RelA; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; C539130:NCOR2 protein, human; D016328:NF-kappa B; D009687:Nuclear Proteins; D056985:Nuclear Receptor Co-Repressor 2; D012097:Repressor Proteins; D015534:Trans-Activators; D051996:Transcription Factor RelA; D012694:Serine; D050882:CREB-Binding Protein; C494363:CREBBP protein, human; C517683:CAMK4 protein, human; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4; D017871:Calcium-Calmodulin-Dependent Protein Kinases