Which phosphatase deactivates mitotic CDKs to promote exit from mitosis?
Lowering mitotic kinase activity requires collaboration between ubiquitin mediated cyclin destruction and phosphatase mediated substrate dephosphorylation. APC/C-Cdc20 degrades cyclin B reducing CDK1 catalytic availability, but hundreds of phosphorylated residues remain. Phosphatases execute erasure. In yeast, Cdc14 is dominant enzyme preferentially dephosphorylating proline-directed CDK sites, including Cdh1 to activate APC/C-Cdh1 for further cyclin clearance, Swi5 for Sic1 transcription and structural cytokinesis proteins. In metazoa, PP2A-B55 family is major mitotic exit phosphatase regulated by Greatwall kinase and its substrates ENSA and Arpp19; when Greatwall inhibited at anaphase onset through cyclin B degradation and PP1 activation, ENSA dephosphorylation releases PP2A-B55 active site allowing dephosphorylation of PRC1, ECT2, Nup53 and other mitotic targets essential for central spindle assembly and nuclear reformation. Dataset annotation assigning CDK1 as phosphatase is inaccurate; CDK1 is kinase itself deactivated during exit. CDC14A/B assist PP2A-B55. Inhibition of these phosphatases preserves hyperphosphorylated state leading to segregated but condensed chromosomes, failure of nuclear envelope reassembly and block of abscission. Additional feedback loops involving polo-like kinases, phosphatases and SCF-mediated degradation reinforce irreversibility and protect against premature progression that would compromise genome integrity and viability.
Ref: Wurzenberger & Gerlich, Mitotic Phosphatases PP2A and Cdc14 in Exit, J Cell Biol 2011; NCBI Bookshelf, Regulation of Mitotic Exit.