Polar gradients of the DYRK-family kinase Pom1 couple cell length with the cell cycle.

Details

Serval ID
serval:BIB_2134FA975036
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Polar gradients of the DYRK-family kinase Pom1 couple cell length with the cell cycle.
Journal
Nature
Author(s)
Martin S.G., Berthelot-Grosjean M.
ISSN
1476-4687 (Electronic)
ISSN-L
0028-0836
Publication state
Published
Issued date
2009
Peer-reviewed
Oui
Volume
459
Number
7248
Pages
852-856
Language
english
Abstract
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.
Keywords
Cell Cycle/physiology, Cell Cycle Proteins/antagonists & inhibitors, Cell Cycle Proteins/metabolism, Cell Polarity, Fungal Proteins/metabolism, G2 Phase, Mitosis, Nuclear Proteins/antagonists & inhibitors, Nuclear Proteins/metabolism, Phosphorylation, Protein Kinases/metabolism, Protein Transport, Protein-Serine-Threonine Kinases/antagonists & inhibitors, Protein-Serine-Threonine Kinases/metabolism, Protein-Tyrosine Kinases/antagonists & inhibitors, Protein-Tyrosine Kinases/metabolism, Schizosaccharomyces/cytology, Schizosaccharomyces/metabolism, Schizosaccharomyces pombe Proteins/antagonists & inhibitors, Schizosaccharomyces pombe Proteins/metabolism, ras-GRF1/metabolism
Pubmed
Web of science
Create date
25/01/2010 11:03
Last modification date
20/08/2019 12:57
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