| Autor: |
Higashitsuji H; Department of Clinical Molecular Biology, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawaharacho, Sakyo-ku, Kyoto 606-8507, Japan. hhigashi@virus.kyoto-u.ac.jp, Higashitsuji H, Liu Y, Masuda T, Fujita T, Abdel-Aziz HI, Kongkham S, Dawson S, John Mayer R, Itoh Y, Sakurai T, Itoh K, Fujita J |
| Jazyk: |
angličtina |
| Zdroj: |
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2007 Nov 23; Vol. 363 (3), pp. 879-84. Date of Electronic Publication: 2007 Sep 29. |
| DOI: |
10.1016/j.bbrc.2007.09.072 |
| Abstrakt: |
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 IkappaBs, we investigated its interaction with NF-kappaB. We found that gankyrin directly binds to RelA. In HeLa and 293 cells, overexpression of gankyrin suppressed the basal as well as TNFalpha-induced transcriptional activity of NF-kappaB, whereas down-regulation of gankyrin increased it. Gankyrin did not affect the NF-kappaB DNA-binding activity or nuclear translocation of RelA induced by TNFalpha in these cells. Leptomycin B that inhibits nuclear export of RelA suppressed the NF-kappaB 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-kappaB and suppresses its activity at the transcription level by modulating acetylation via SIRT1. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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