IKKα regulates the mitotic phase of the cell cycle by modulating Aurora A phosphorylation

The IKK complex includes two catalytic components, IKK alpha and IKK beta, in addition to the scaffold protein IKK gamma/NEMO. Even though IKK alpha and IKK beta share significant sequence homology, they have distinct biological roles with IKK beta regulates the classical pathway of NF-kappa B activation and IKK alpha regulates the alternative pathways. In addition, it has been shown that the IKKs regulate the proliferation of both normal and tumor cells; however, the mechanisms by which the IKKs regulate the cell cycle remain to be further defined. Here, we demonstrate that IKK alpha, but not IKK beta, has role in regulating the M phase of the cell cycle. IKK alpha siRNA knock-down resulted in increased numbers of cells in the G(2)/M phase of the cell cycle as compared to control and IKK beta siRNA transfected HeLa cells. This effect was associated with upregulation of cyclin B1 and Plk1 protein levels and increased histone H3 phosphorylation, consistent with a potential role of IKK alpha in the regulation of M phase regulatory factors. IKK alpha was found to be associated with Aurora A in the centrosome and regulate Aurora A phosphorylation at threonine residue 288, a site which is important in modulating its kinase activity. Taken together, these data provide the evidence that IKK alpha regulates the M phase of the cell cycle by modulating Aurora A phosphorylation and activation leading to the regulation of the M phase of the cell cycle.