The oncoprotein gankyrin interacts with RelA and suppresses NF-κB activity
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- 作者：Hiroaki Higashitsuji ; Hisako Higashitsuji ; Yu Liu ; Tomoko Masuda ; Takanori Fujita ; H. Ismail Abdel-Aziz ; Supranee Kongkham ; Simon Dawson ; R. John Mayer ; Yoshito Itoh ; Toshiharu Sakurai ; Katsuhiko Itoh
- 关键词：PSMD10 ; NF-κ ; B ; HSCO ; Ankyrin ; Histone deacetylase
- 刊名：Biochemical and Biophysical Research Communications
- 出版年：2007
- 出版时间：23 November 2007
- 年：2007
- 卷：363
- 期：3
- 页码：879-884
- 全文大小：573 K
文摘
Gankyrin is an oncoprotein commonly overexpressed in hepatocellular carcinomas. It interacts with multiple proteins and accelerates degradation of tumor suppressors Rb and p53. Since gankyrin consists of 7 ankyrin repeats and is structurally similar to IκBs, we investigated its interaction with NF-κB. We found that gankyrin directly binds to RelA. In HeLa and 293 cells, overexpression of gankyrin suppressed the basal as well as TNFα-induced transcriptional activity of NF-κB, whereas down-regulation of gankyrin increased it. Gankyrin did not affect the NF-κB DNA-binding activity or nuclear translocation of RelA induced by TNFα in these cells. Leptomycin B that inhibits nuclear export of RelA suppressed the NF-κB activity, which was further suppressed by gankyrin. The inhibitory effect of gankyrin was abrogated by nicotinamide as well as down-regulation of SIRT1, a class III histone deacetylase. Thus, gankyrin binds to NF-κB and suppresses its activity at the transcription level by modulating acetylation via SIRT1.