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Phosphorylation by Cyclin B-Cdk Underlies Release of Mitotic Exit Activator Cdc14 from the Nucleolus

Azzam, Ramzi and Chen, Susan L. and Shou, Wenying and Mah, Angie S. and Alexandru, Gabriela and Nasmyth, Kim and Annan, Roland S. and Carr, Steven A. and Deshaies, Raymond J. (2004) Phosphorylation by Cyclin B-Cdk Underlies Release of Mitotic Exit Activator Cdc14 from the Nucleolus. Science, 305 (5683). pp. 516-519. ISSN 0036-8075. doi:10.1126/science.1099402.

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Budding yeast protein phosphatase Cdc14 is sequestered in the nucleolus in an inactive state during interphase by the anchor protein Net1. Upon entry into anaphase, the Cdc14 early anaphase release (FEAR) network initiates dispersal of active Cdc14 throughout the cell. We report that the FEARnetwork promotes phosphorylation of Net1 by cyclin-dependent kinase (Cdk) complexed with cyclin B1 or cyclin B2. These phosphorylations appear to be required for FEAR and sustain the proper timing of late mitotic events. Thus, a regulatory circuit exists to ensure that the arbiter of the mitotic state, Cdk, sets in motion events that culminate in exit from mitosis.

Item Type:Article
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URLURL TypeDescription DOIArticle Information
Carr, Steven A.0000-0002-7203-4299
Deshaies, Raymond J.0000-0002-3671-9354
Additional Information:© 2004 American Association for the Advancement of Science. 21 April 2004; accepted 25 June 2004. We thank J. Huangh for the Net1 1-621 construct; I. Lesur for help with elutriation; D. Kellogg for antibody to Clb2; K. Shokat for NaPP1 analog; the Morgan, Amon, and Holloway labs for various strains and GAL1p-CLB2 mutant constructs; M. Olson for the Clb2-MBP bacterial construct; R. Verma for preparing the Baculo (GST-Cdc28-HA) virus; M. Petroski for purified Clb5-Cdk; J. Graumann for mass spectrometry analysis; J. Sanders for mutagenesis efforts; and members of the Deshaies lab for critical comments during the course of this work. Supported by NIH grant GM59940 (R.J.D.) and by fellowships from the Norris and Baxter foundations (R.A.). R.J.D. is an Assistant Investigator of the Howard Hughes Medical Institute. Molecular interaction data have been deposited in the Biomolecular Interaction Network Database with accession codes 145590 and 145624.
Funding AgencyGrant Number
Kenneth T. and Eileen L. Norris FoundationUNSPECIFIED
Baxter FoundationUNSPECIFIED
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Issue or Number:5683
Record Number:CaltechAUTHORS:20141118-095256128
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Official Citation:Azzam, R., Chen, S. L., Shou, W., Mah, A. S., Alexandru, G., Nasmyth, K., . . . Deshaies, R. J. (2004). Phosphorylation by Cyclin B-Cdk Underlies Release of Mitotic Exit Activator Cdc14 from the Nucleolus. Science, 305(5683), 516-519. doi: 10.1126/science.1099402
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:51890
Deposited On:18 Nov 2014 19:27
Last Modified:10 Nov 2021 19:17

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