CaMKII phosphorylates serine 10 of p27 and confers apoptosis resistance to HeLa cells

Protein phosphatase (PP) 6 is a serine threonine phosphatase which belongs to the PP2A subfamily of protein phosphatases. PP6 has been implicated in the control of apoptosis. A dominant negative form PP6 (DN-PP6) mutant cDNA was prepared and transfected into HeLa cells to investigate the regulation of apoptosis. HeLa cells expressing DN-PP6 showed increased resistance to apoptosis induced by TNF and cycloheximide. CaMKII phosphorylation and the expression of p27 were increased in DN-PP6 transfectants. Transient expression or activation of CaMKII increased the expression of p27. Furthermore, CaMKII phosphorylated serine 10 of p27, which induces the translocation of p27 from nucleus to cytoplasm and increases the stability of p27. Overexpression of wild type but not the S10A mutant p27 cDNA increased the expression of Bcl-xL and conferred apoptosis resistance to HeLa cells. These results indicated that PP6 and CaMKII regulated apoptosis by controlling the expression level of p27.

Research highlights
► Establishment of a dominant negative form cDNA of protein phosphatase 6 (DN-PP6).
► The overexpression of DN-PP6 results in apoptosis resistance in HeLa cells.
► CaMKII phosphorylates serine 10 of p27 and translocates p27 to cytoplasm.
► An increased expression of cytoplasmic p27 is responsible for apoptosis resistance.