The oncoprotein gankyrin interacts with RelA and suppresses NF-{kappa}B activity

Journal Article · Fri Nov 23 04:00:00 EST 2007 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/j.bbrc.2007.09.072· OSTI ID:21032990

Higashitsuji, Hiroaki ^[1]; Higashitsuji, Hisako; Liu, Yu; Masuda, Tomoko; Fujita, Takanori; Abdel-Aziz, H Ismail ^[1]; Kongkham, Supranee; Dawson, Simon; John Mayer, R ^[2]; Itoh, Yoshito ^[3]; Sakurai, Toshiharu; Itoh, Katsuhiko ^[1]; Fujita, Jun ^[1]

---

1. Department of Clinical Molecular Biology, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawaharacho, Sakyo-ku, Kyoto 606-8507 (Japan)
2. Laboratory of Intracellular Proteolysis, School of Biomedical Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham NG7 2UH (United Kingdom)
3. Molecular Gastroenterology and Hepatology, Graduate School of Medical Sciences, Kyoto Prefectural University of Medicine, Kyoto 602-8566 (Japan)

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 I{kappa}Bs, we investigated its interaction with NF-{kappa}B. We found that gankyrin directly binds to RelA. In HeLa and 293 cells, overexpression of gankyrin suppressed the basal as well as TNF{alpha}-induced transcriptional activity of NF-{kappa}B, whereas down-regulation of gankyrin increased it. Gankyrin did not affect the NF-{kappa}B DNA-binding activity or nuclear translocation of RelA induced by TNF{alpha} in these cells. Leptomycin B that inhibits nuclear export of RelA suppressed the NF-{kappa}B 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-{kappa}B and suppresses its activity at the transcription level by modulating acetylation via SIRT1.

• OSTI ID: 21032990
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 3 Vol. 363; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ACETYLATION
DNA
ELECTROPHORESIS
GENE REGULATION
HEPATOMAS
NICOTINAMIDE
TRANSCRIPTION
TRANSLOCATION