Centrosomal P4.1-associated protein is a new member of transcriptional coactivators for nuclear factor-κB

被引:31
作者
Koyanagi, M [1 ]
Hijikata, M [1 ]
Watashi, K [1 ]
Masui, O [1 ]
Shimotohno, K [1 ]
机构
[1] Kyoto Univ, Inst Virus Res, Dept Viral Oncol, Sakyo Ku, Kyoto 6068507, Japan
关键词
D O I
10.1074/jbc.M410420200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Nuclear factor-kappa B ( NF-kappa B) is a transcription factor important for various cellular events such as inflammation, immune response, proliferation, and apoptosis. In this study, we performed a yeast two-hybrid screening using the N-terminal domain of the p65 subunit ( RelA) of NF-kappa B as bait and isolated centrosomal P4.1-associated protein ( CPAP) as a candidate for a RelA-associating partner. Glutathione S-transferase pull-down assays and co-immunoprecipitation experiments followed by Western blotting also showed association of CPAP with RelA. When overexpressed, CPAP enhanced NF-kappa B- dependent transcription induced by tumor necrosis factor-alpha (TNF alpha). Reduction of the protein level of endogenous CPAP by RNA interference resulted in decreased activation of NF-kappa B by TNF alpha. After treatment with TNF alpha, a portion of CPAP was observed to accumulate in the nucleus, although CPAP was found primarily in the cytoplasm without any stimulation. Moreover, CPAP was observed in a complex recruited to the transcriptional promoter region containing the NF-kappa B-binding motif. One hybrid assay showed that CPAP has the potential to activate gene expression when tethered to the transcriptional promoter. These data suggest that CPAP functions as a coactivator of NF-kappa B-mediated transcription. Since a physiological interaction between CPAP and the coactivator p300/CREB-binding protein was also observed and synergistic activation of NF-kappa B- mediated transcription was achieved by these proteins, CPAP-dependent transcriptional activation is likely to include p300/CREB-binding protein.
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页码:12430 / 12437
页数:8
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