Document Detail


Polar gradients of the DYRK-family kinase Pom1 couple cell length with the cell cycle.
MedLine Citation:
PMID:  19474792     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cells normally grow to a certain size before they enter mitosis and divide. Entry into mitosis depends on the activity of Cdk1, which is inhibited by the Wee1 kinase and activated by the Cdc25 phosphatase. However, how cells sense their size for mitotic commitment remains unknown. Here we show that an intracellular gradient of the dual-specificity tyrosine-phosphorylation regulated kinase (DYRK) Pom1, which emanates from the ends of rod-shaped Schizosaccharomyces pombe cells, serves to measure cell length and control mitotic entry. Pom1 provides positional information both for polarized growth and to inhibit cell division at cell ends. We discovered that Pom1 is also a dose-dependent G2-M inhibitor. Genetic analyses indicate that Pom1 negatively regulates Cdr1 and Cdr2, two previously described Wee1 inhibitors of the SAD kinase family. This inhibition may be direct, because in vivo and in vitro evidence suggest that Pom1 phosphorylates Cdr2. Whereas Cdr1 and Cdr2 localize to a medial cortical region, Pom1 forms concentration gradients from cell tips that overlap with Cdr1 and Cdr2 in short cells, but not in long cells. Disturbing these Pom1 gradients leads to Cdr2 phosphorylation and imposes a G2 delay. In short cells, Pom1 prevents precocious M-phase entry, suggesting that the higher medial Pom1 levels inhibit Cdr2 and promote a G2 delay. Thus, gradients of Pom1 from cell ends provide a measure of cell length to regulate M-phase entry.
Authors:
Sophie G Martin; Martine Berthelot-Grosjean
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-05-27
Journal Detail:
Title:  Nature     Volume:  459     ISSN:  1476-4687     ISO Abbreviation:  Nature     Publication Date:  2009 Jun 
Date Detail:
Created Date:  2009-06-11     Completed Date:  2009-08-05     Revised Date:  2009-12-11    
Medline Journal Info:
Nlm Unique ID:  0410462     Medline TA:  Nature     Country:  England    
Other Details:
Languages:  eng     Pagination:  852-6     Citation Subset:  IM    
Affiliation:
Center for Integrative Genomics, Faculty of Biology and Medicine, University of Lausanne, Génopode Building, 1015 Lausanne, Switzerland. Sophie.Martin@unil.ch
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MeSH Terms
Descriptor/Qualifier:
Cell Cycle / physiology*
Cell Cycle Proteins / antagonists & inhibitors,  metabolism
Cell Polarity*
Fungal Proteins / metabolism
G2 Phase
Mitosis
Nuclear Proteins / antagonists & inhibitors,  metabolism
Phosphorylation
Protein Kinases / metabolism*
Protein Transport
Protein-Serine-Threonine Kinases / antagonists & inhibitors,  metabolism
Protein-Tyrosine Kinases / antagonists & inhibitors,  metabolism
Schizosaccharomyces / cytology*,  metabolism*
Schizosaccharomyces pombe Proteins / antagonists & inhibitors,  metabolism
ras-GRF1 / metabolism
Chemical
Reg. No./Substance:
0/Cell Cycle Proteins; 0/Fungal Proteins; 0/Nuclear Proteins; 0/Schizosaccharomyces pombe Proteins; 0/cdc22 protein, S pombe; 0/ras-GRF1; EC 2.7.-/Protein Kinases; EC 2.7.1.-/Pom1 protein, S pombe; EC 2.7.1.-/cdr1 protein, S pombe; EC 2.7.1.-/wee1 protein, S pombe; EC 2.7.10.1/Protein-Tyrosine Kinases; EC 2.7.11.1/Cdr2 protein, S pombe; EC 2.7.11.1/Protein-Serine-Threonine Kinases
Comments/Corrections
Comment In:
Nature. 2009 Jun 11;459(7248):782-3   [PMID:  19516326 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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