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  • Title: Krüppel-associated box-associated protein 1 negatively regulates TNF-α-induced NF-κB transcriptional activity by influencing the interactions among STAT3, p300, and NF-κB/p65.
    Author: Kamitani S, Togi S, Ikeda O, Nakasuji M, Sakauchi A, Sekine Y, Muromoto R, Oritani K, Matsuda T.
    Journal: J Immunol; 2011 Sep 01; 187(5):2476-83. PubMed ID: 21810609.
    Abstract:
    Krüppel-associated box-associated protein 1 (KAP1) is thought to act mainly as a scaffold for protein complexes, which together silence transcription by triggering the formation of heterochromatin. Using small interfering RNA-mediated KAP1 knockdown, we found that endogenous KAP1 negatively regulated TNF-α-induced IL-6 production in HeLa cells. KAP1 is likely to modulate the binding of NF-κB to the IL-6 promoter because KAP1 knockdown enhanced TNF-α-induced NF-κB-luciferase activity, but not IκBα degradation. Of importance, we found negative regulatory effects of KAP1 on the serine phosphorylation of STAT3, the acetylation of NF-κB/p65 by p300, and the nuclear localization of NF-κB/p65. In addition, KAP1 associated with NF-κB/p65 and inhibited the binding between NF-κB/p65 and p300. Thus, KAP1 is likely to negatively control the acetylation of NF-κB/p65, which is critical for its nuclear retention. Taken together, KAP1 modulated the acetylation of NF-κB/p65 by interfering with the interactions among STAT3, p300, and NF-κB/p65, resulting in reduced IL-6 production after TNF-α stimulation. Our findings that KAP1 directly interacts with transcriptional factors are new, and will inform further research to elucidate KAP1 function.
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