Akt-mediated regulation of NFκB and the essentialness of NFκB for the oncogenicity of PI3K and Akt
作者： Dong Bai , Lynn Ueno , Peter K. Vogt
DOI: 10.1002/IJC.24748
关键词:
摘要: The serine/threonine kinase Akt (cellular homolog of murine thymoma virus akt8 oncogene), also known as PKB (protein B), is activated by lipid products phosphatidylinositol 3-kinase (PI3K). phosphorylates numerous protein targets that control cell survival, proliferation and motility. Previous studies suggest regulates transcriptional activity the nuclear factor-kappaB (NFkappaB) inducing phosphorylation subsequent degradation inhibitor kappaB (IkappaB). We show here NFkappaB-driven transcription increases in chicken embryonic fibroblasts (CEF) transformed myristylated (myrAkt). Accordingly, both a dominant negative mutant inhibitors repress NFkappaB-dependent transcription. IkappaB strongly enhanced Akt-transformed cells, loss NFkappaB introduction super-repressor NFkappaB, IkappaBSR, interferes with PI3K- Akt-induced oncogenic transformation CEF. p65 subunit at serine 534 upregulated cells. Our data stimulation dependent on S534, mediated IKK (IkappaB kinase) alpha beta. IKKalpha T23, this event prerequisite for S534 results demonstrate two separate functions complex activation cells constitutive activity: consequent p65. further support conclusion essential transformation.
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