The Localization of Human Cyclins B1 and B2 Determines CDK1 Substrate Specificity and Neither Enzyme Requires MEK to Disassemble the Golgi Apparatus

doi:10.1083/jcb.152.5.945

Published online 5 March 2001. doi:10.1083/jcb.152.5.945

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© The Rockefeller University Press, 0021-9525/2001/3/945/ $5.00
The Journal of Cell Biology, Volume 152, Number 5, March 5, 2001 945-958

Original Article

The Localization of Human Cyclins B1 and B2 Determines CDK1 Substrate Specificity and Neither Enzyme Requires MEK to Disassemble the Golgi Apparatus

Viji Mythily Draviam^a, Simona Orrechia^b, Martin Lowe^c, Ruggero Pardi^b, and Jonathon Pines^a
^a Wellcome/Cancer Research Campaign Institute and Department of Zoology, Cambridge CB2 1QR, United Kingdom
^b Vita Salute University School of Medicine, Scientific Institute San Raffaele, Milan I-20132, Italy
^c Division of Biochemistry, School of Biological Sciences, University of Manchester, Manchester M13 9PT, United Kingdom

Correspondence to: Jonathon Pines, Wellcome/CRC Institute, Department of Zoology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK. Tel:44-1223-33-4096 Fax:44-1223-33-4089 E-mail:jp103{at}mole.bio.cam.ac.uk.

In this paper, we show that substrate specificity is primarilyconferred on human mitotic cyclin-dependent kinases (CDKs) bytheir subcellular localization. The difference in localizationof the B-type cyclin–CDKs underlies the ability of cyclinB1–CDK1 to cause chromosome condensation, reorganizationof the microtubules, and disassembly of the nuclear lamina andof the Golgi apparatus, while it restricts cyclin B2–CDK1to disassembly of the Golgi apparatus. We identify the regionof cyclin B2 responsible for its localization and show thatthis will direct cyclin B1 to the Golgi apparatus and conferupon it the more limited properties of cyclin B2. Equally, directingcyclin B2 to the cytoplasm with the NH₂ terminus of cyclin B1confers the broader properties of cyclin B1. Furthermore, weshow that the disassembly of the Golgi apparatus initiated byeither mitotic cyclin–CDK complex does not require mitogen-activatedprotein kinase kinase (MEK) activity.

Key Words: cyclin, CDK, mitosis, protein kinase, Golgi apparatus

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