The localization of human cyclins B1 and B2 determines CDK1 substrate specificity and neither enzyme requires MEK to disassemble the Golgi apparatus.
In this paper, we show that substrate specificity is primarily conferred on human mitotic cyclin-dependent kinases (CDKs) by their subcellular localization. The difference in localization of the B-type cyclin-CDKs underlies the ability of cyclin B1-CDK1 to cause chromosome condensation, reorganization of the microtubules, and disassembly of the nuclear lamina and of the Golgi apparatus, while it restricts cyclin B2-CDK1 to disassembly of the Golgi apparatus. We identify the region of cyclin B2 responsible for its localization and show that this will direct cyclin B1 to the Golgi apparatus and confer upon it the more limited properties of cyclin B2. Equally, directing cyclin B2 to the cytoplasm with the NH(2) terminus of cyclin B1 confers the broader properties of cyclin B1. Furthermore, we show that the disassembly of the Golgi apparatus initiated by either mitotic cyclin-CDK complex does not require mitogen-activated protein kinase kinase (MEK) activity.
Wellcome/Cancer Research Campaign Institute and Department of Zoology, Cambridge CB2 1QR, United Kingdom.
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Draviam
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Orrechia
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Lowe
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Pardi
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Pines
D000818:Animals; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D016466:CHO Cells; D002875:Chromosomes / Q000378:metabolism; D006224:Cricetinae; D019926:Cyclin B / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D056744:Cyclin B1; D056765:Cyclin B2; D003599:Cytoskeleton / Q000378:metabolism; D016193:G1 Phase; D006056:Golgi Apparatus / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008938:Mitosis; D011494:Protein Kinases / Q000378:metabolism; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D016192:Resting Phase, Cell Cycle; D013379:Substrate Specificity
C534699:CCNB1 protein, human; C503758:CCNB2 protein, human; D019926:Cyclin B; D056744:Cyclin B1; D056765:Cyclin B2; D011993:Recombinant Fusion Proteins; D011494:Protein Kinases; C102333:histone H1 kinase; D016203:CDC2 Protein Kinase; D020929:Mitogen-Activated Protein Kinase Kinases