Ordered dephosphorylation initiated by the selective proteolysis of cyclin B drives mitotic exit

eLife

Shabaz Mohammed¹  James Holder¹  Francis A Barr¹ 

[1] Department of Biochemistry, University of Oxford, Oxford, United Kingdom;

关键词: dephosphorylation;    proteolysis;    APC/C;    PP1;    mitotic exit;    cell cycle;   

DOI  :  10.7554/eLife.59885

来源: DOAJ

【 摘 要 】

APC/C-mediated proteolysis of cyclin B and securin promotes anaphase entry, inactivating CDK1 and permitting chromosome segregation, respectively. Reduction of CDK1 activity relieves inhibition of the CDK1-counteracting phosphatases PP1 and PP2A-B55, allowing wide-spread dephosphorylation of substrates. Meanwhile, continued APC/C activity promotes proteolysis of other mitotic regulators. Together, these activities orchestrate a complex series of events during mitotic exit. However, the relative importance of regulated proteolysis and dephosphorylation in dictating the order and timing of these events remains unclear. Using high temporal-resolution proteomics, we compare the relative extent of proteolysis and protein dephosphorylation. This reveals highly-selective rapid proteolysis of cyclin B, securin and geminin at the metaphase-anaphase transition, followed by slow proteolysis of other substrates. Dephosphorylation requires APC/C-dependent destruction of cyclin B and was resolved into PP1-dependent categories with unique sequence motifs. We conclude that dephosphorylation initiated by selective proteolysis of cyclin B drives the bulk of changes observed during mitotic exit.

【 授权许可】

Unknown