Inhibition of NF-kappaB acetylation and its transcriptional activity by Daxx.
We propose a biochemical mechanism by which Daxx modulates NF-kappaB transcriptional activity. Both chromatin immunoprecipitation (ChIP) assay and electrophoretic mobility shift assay (EMSA) have confirmed Daxx-mediated repression of transcriptional competence of NF-kappaB in HeLa cells. Overexpression of Daxx repressed the expression of NF-kappaB-regulated genes such as I kappa B alpha and IL8. Co-immunoprecipitation assay revealed the existence of intermolecular association between endogenous Daxx and p65 subunit of NF-kappaB stimulated by TNFalpha. Here, we suggest that Daxx-mediated repression of NF-kappaB transactivation correlates with the inhibition of p65 acetylation by Daxx. Based on the finding that the Daxx binding N-terminal side of p65 includes the major sites of acetylation mediated by p300/CBP, we further propose that the physical interaction between Daxx and p65 provides a functional framework for the inhibition of p65 acetylation by p300/CBP and subsequent repression of NF-kappaB transcriptional activity.
Park
Jinhwi
J
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, 305-701, South Korea.
Lee
Jae Ho
JH
La
Muhnho
M
Jang
Moon Jung
MJ
Chae
Gil Woo
GW
Kim
Seung Beom
SB
Tak
Heejae
H
Jung
Yunhwa
Y
Byun
Boohyeong
B
Ahn
Jeong Keun
JK
Joe
Cheol O
CO
D000107:Acetylation; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D056970:Co-Repressor Proteins; D050881:E1A-Associated p300 Protein / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D018832:Molecular Chaperones; D009687:Nuclear Proteins / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D021381:Protein Transport; D013347:Subcellular Fractions / Q000378:metabolism; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation / Q000235:genetics*
D048868:Adaptor Proteins, Signal Transducing; D056970:Co-Repressor Proteins; C106985:DAXX protein, human; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D051996:Transcription Factor RelA; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human