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 NH2 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.
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5 March 2001
Article|
March 05 2001
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,
Viji Mythily Draviam
aWellcome/Cancer Research Campaign Institute and Department of Zoology, Cambridge CB2 1QR, United Kingdom
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Simona Orrechia,
Simona Orrechia
bVita Salute University School of Medicine, Scientific Institute San Raffaele, Milan I-20132, Italy
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Martin Lowe,
Martin Lowe
cDivision of Biochemistry, School of Biological Sciences, University of Manchester, Manchester M13 9PT, United Kingdom
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Ruggero Pardi,
Ruggero Pardi
bVita Salute University School of Medicine, Scientific Institute San Raffaele, Milan I-20132, Italy
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Jonathon Pines
Jonathon Pines
aWellcome/Cancer Research Campaign Institute and Department of Zoology, Cambridge CB2 1QR, United Kingdom
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Viji Mythily Draviam
aWellcome/Cancer Research Campaign Institute and Department of Zoology, Cambridge CB2 1QR, United Kingdom
Simona Orrechia
bVita Salute University School of Medicine, Scientific Institute San Raffaele, Milan I-20132, Italy
Martin Lowe
cDivision of Biochemistry, School of Biological Sciences, University of Manchester, Manchester M13 9PT, United Kingdom
Ruggero Pardi
bVita Salute University School of Medicine, Scientific Institute San Raffaele, Milan I-20132, Italy
Jonathon Pines
aWellcome/Cancer Research Campaign Institute and Department of Zoology, Cambridge CB2 1QR, United Kingdom
Abbreviations used in this paper: CDK, cyclin-dependent kinase; ERK, extracellular singal–regulated kinase; GFP, green fluorescent protein; LMB, leptomycin B; MAP, mitogen-activated protein; MEK, MAP kinase kinase; NAGT, N-acetyglucosaminyltransferase 1.
Received:
November 28 2000
Revision Requested:
December 19 2000
Accepted:
January 18 2001
Online ISSN: 1540-8140
Print ISSN: 0021-9525
© 2001 The Rockefeller University Press
2001
The Rockefeller University Press
J Cell Biol (2001) 152 (5): 945–958.
Article history
Received:
November 28 2000
Revision Requested:
December 19 2000
Accepted:
January 18 2001
Citation
Viji Mythily Draviam, Simona Orrechia, Martin Lowe, Ruggero Pardi, Jonathon Pines; The Localization of Human Cyclins B1 and B2 Determines Cdk1 Substrate Specificity and Neither Enzyme Requires Mek to Disassemble the Golgi Apparatus. J Cell Biol 5 March 2001; 152 (5): 945–958. doi: https://doi.org/10.1083/jcb.152.5.945
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