MAPK6 is hyperphosphorylated by CDK1 at multiple sites in the C-terminal extension, and this phosphorylation is associated with the stabilization of MAPK6 protein in mitosis. Residues S684, S688, T698 and S705 have been identified as in vitro targets of CDK1, and phosphorylation of T698 has also been demonstrated in vivo (Tanguay et al, 2010). The role of hyperphosphorylated MAPK6 during mitosis has not been established, and although the CDK1-dependent phosphorylation of MAPK6 is depicted as occuring in the nucleus, the site of action has also not been determined. CDK1-dependent hyperphosphorylation of the C-terminal tail is reversed by the phosphatases CDC14A and B (Tanguay et al, 2010; Hansen et al, 2008).