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.
Kajihara
Ryutaro
R
Department of Immunology and Hematology, Division of Health Sciences, Faculty of Life Sciences, Kumamoto University, Japan.
Fukushige
Shota
S
Shioda
Norifumi
N
Tanabe
Kano
K
Fukunaga
Kohji
K
Inui
Seiji
S
D000595:Amino Acid Sequence; D017209:Apoptosis; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism*; D018076:DNA, Complementary / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D012694:Serine / Q000235:genetics / Q000378:metabolism*; D051020:bcl-X Protein / Q000378:metabolism
C494811:BCL2L1 protein, human; D018076:DNA, Complementary; D051020:bcl-X Protein; D050760:Cyclin-Dependent Kinase Inhibitor p27; D012694:Serine; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D010749:Phosphoprotein Phosphatases; C106079:protein phosphatase 6