Complex formation of p65/RelA with nuclear Akt1 for enhanced transcriptional activation of NF-{kappa}B

• Published in: Biochemical and biophysical research communications 2008-01, Vol.365 (4)
• Main Authors: Kwon, Osong, Kim, Kyung A, He, Long, Jung, Mira, Jeong, Sook Jung, Ahn, Jong Seog, Kim, Bo Yeon
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; CELL NUCLEI; COMPLEXES; CYTOPLASM; INHIBITION; MUTANTS; PROSTATE; SULFIDES
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2007.11.037

Akt1 was revealed to interact with Ki-Ras in the cytoplasm of Ki-Ras-transformed human prostate epithelial cells, 267B1/K-ras. Moreover, p65/RelA in the nucleus was found to interact with both Ki-Ras and Akt1, suggesting the nuclear translocation of Akt1:Ki-Ras complex for NF- {kappa}B activation. In support of this, compared with wild type Akt1, the dominant negative Akt1 mutant was decreased in its nuclear expression, reducing the Ki-Ras-induced NF-{kappa}B transcriptional activation. Moreover, inhibitors of Ras (sulindac sulfide and farnesyltransferase inhibitor I) or PI3K/Akt (wortmannin), reduced the amounts of Akt1 and Ki-Ras in the nucleus as well as partial NF-{kappa}B activity. The complete inhibition of Ki-Ras-induced NF-{kappa}B activation, however, could only be obtained by combined treatment with wortmannin and proteasome inhibitor-1. Accordingly, clonogenic assay showed Akt1 contribution to I{kappa}B{alpha}-mediated NF-{kappa}B activation for oncogenic cell growth by Ki-Ras. Our data suggest a crucial role of Ki-Ras:Akt1 complex in NF-{kappa}B transcriptional activation and enhancement of cell survival.