Securin regulates entry into M-phase by modulating the stability of cyclin B.
Timely progression into mitosis is necessary for normal cell division. This transition is sensitive to the levels of cyclin B, the regulatory subunit of the master mitotic kinase, Cdk1. Cyclin B accumulates during G2 and prophase when its rate of destruction by the anaphase promoting complex (APC) is low. Securin is also an APC substrate and is known for its role in inactivating the cohesin-cleaving enzyme, separase, until the metaphase to anaphase transition. Here we show that securin has an additional role in cell-cycle regulation, that of modulating the timing of entry into M-phase. In mouse oocytes, excess securin caused stabilization of cyclin B and precocious entry into M-phase. Depletion of securin increased cyclin B degradation, resulting in delayed progression into M-phase. This effect required APC activity and was reversed by expression of wild-type securin. These data reveal a role for securin at the G2-M transition and suggest a more general mechanism whereby physiological levels of co-competing APC substrates function in modulating the timing of cell-cycle transitions.
Marangos
Petros
P
Department of Cell and Developmental Biology, Division of Biosciences, University College London, Gower Street, London, WC1E 6BT, UK. p.marangos@ucl.ac.uk
Carroll
John
J
D000818:Animals; D064127:Aurora Kinases; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division / Q000502:physiology*; D002478:Cells, Cultured; D019926:Cyclin B / Q000235:genetics / Q000378:metabolism*; D056744:Cyclin B1; D005260:Female; D006801:Humans; D051379:Mice; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000378:metabolism; D009865:Oocytes / Q000166:cytology / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D064249:Securin
C534699:CCNB1 protein, human; D002352:Carrier Proteins; C534700:Ccnb1 protein, mouse; D019926:Cyclin B; D056744:Cyclin B1; D016376:Oligonucleotides, Antisense; D011993:Recombinant Fusion Proteins; D064249:Securin; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases