The oncoprotein gankyrin interacts with RelA and suppresses NF-κB activity
- 23 November 2007
- journal article
- Published by Elsevier BV in Biochemical and Biophysical Research Communications
- Vol. 363 (3), 879-884
- https://doi.org/10.1016/j.bbrc.2007.09.072
Abstract
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.Keywords
This publication has 17 references indexed in Scilit:
- Inhibition of NF-κB Acetylation and its Transcriptional Activity by DaxxJournal of Molecular Biology, 2007
- Deletion of NEMO/IKKγ in Liver Parenchymal Cells Causes Steatohepatitis and Hepatocellular CarcinomaCancer Cell, 2007
- Post-translational modifications regulating the activity and function of the nuclear factor kappa B pathwayOncogene, 2006
- The Oncoprotein Gankyrin Negatively Regulates Both p53 and RB by Enhancing Proteasomal DegradationCell Cycle, 2005
- The oncoprotein gankyrin binds to MDM2/HDM2, enhancing ubiquitylation and degradation of p53Cancer Cell, 2005
- PIAS3 Suppresses NF-κB-mediated Transcription by Interacting with the p65/RelA SubunitPublished by Elsevier BV ,2004
- Inhibition of Silencing and Accelerated Aging by Nicotinamide, a Putative Negative Regulator of Yeast Sir2 and Human SIRT1Published by Elsevier BV ,2002
- A novel protein overexpressed in hepatoma accelerates export of NF-κB from the nucleus and inhibits p53-dependent apoptosisCancer Cell, 2002
- Missing Pieces in the NF-κB PuzzleCell, 2002
- IκB Family Members Function by Different MechanismsJournal of Biological Chemistry, 2001