Erk5 is activated and acts as a survival factor in mitosis.
Erk5 is a recently discovered MAPK claimed to be responsible for some of the roles attributed to Erk1/2; here we report that it is activated in mitosis in comparison to G1/S. When Erk5 is inactivated pharmacologically or largely ablated by RNAi, cell survival in mitosis is diminished. We have previously shown Bim, a BH3-only protein of the Bcl-2 family, to be phosphorylated in mitosis, in a MEK-dependent manner (M. Grãos, A. D. Almeida, S. Chatterjee, Biochem. J. 388 (2005) 185). Inactivation of Erk5 in mitosis causes dephosphorylation of Bim. Bim is in the mitochondria in mitosis and when dephosphorylated interacts with Bax, inducing caspase activation. We also show that in mitosis Bim co-immunoprecipitates with Erk5 and Erk5 phosphorylates GST-Bim in in vitro kinase reaction. Taken together, our results identify a new target of the still largely mysterious Erk5 and suggest that Erk5 in mitosis may be a decisive step for the survival of proliferating cells.
Gírio
Ana
A
Instituto Gulbenkian de Ciência, Rua da Quinta Grande, 6, 2780-156 Oeiras, Portugal.
Montero
Juan Carlos
JC
Pandiella
Atanasio
A
Chatterjee
Sukalyan
S
D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D000072224:Bcl-2-Like Protein 11; D053179:Caspase 7 / Q000378:metabolism; D016923:Cell Death; D002470:Cell Survival; D004789:Enzyme Activation; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D048054:Mitogen-Activated Protein Kinase 7 / Q000378:metabolism*; D008938:Mitosis; D008954:Models, Biological; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D013379:Substrate Specificity; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; C000606775:BCL2L11 protein, human; D000072224:Bcl-2-Like Protein 11; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D051028:bcl-2-Associated X Protein; D048054:Mitogen-Activated Protein Kinase 7; D053179:Caspase 7