Home LiteratureArticle Details
PMID: 9843572 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

The protein kinase Cdr2, related to Nim1/Cdr1 mitotic inducer, regulates the onset of mitosis in fission yeast.

Molecular biology of the cell ·Vol. 9 ·No. 12 ·1998-12-00 ·Pages 3321-34

Kanoh J, Russell P

Abstract

Cdc2-Cyclin B, the protein kinase that catalyzes the onset of mitosis, is subject to multiple forms of regulation. In the fission yeast Schizosaccharomyces pombe and most other species, a key mode of Cdc2-Cyclin B regulation is the inhibitory phosphorylation of Cdc2 on tyrosine-15. This phosphorylation is catalyzed by the protein kinases Wee1 and Mik1 and removed by the phosphatase Cdc25. These proteins are also regulated, a notable example being the inhibition of Wee1 by the protein kinase Nim1/Cdr1. The temperature-sensitive mutation cdc25-22 is synthetic lethal with nim1/cdr1 mutations, suggesting that a synthetic lethal genetic screen could be used to identify novel mitotic regulators. Here we describe that such a screen has identified cdr2(+), a gene that has an important role in the mitotic control. Cdr2 is a 775 amino acid protein kinase that is closely related to Nim1 and mitotic control proteins in budding yeast. Deletion of cdr2 causes a G2-M delay that is more severe than that caused by nim1/cdr1 mutations. Genetic studies are consistent with a model in which Cdr2 negatively regulates Wee1. This model is supported by experiments showing that Cdr2 associates with the N-terminal regulatory domain of Wee1 in cell lysates and phosphorylates Wee1 in vitro. Thus, Cdr2 is a novel mitotic control protein that appears to regulate Wee1.

MeSH Terms
ATP-Binding Cassette Transporters/genetics,metabolism Amino Acid Sequence Base Sequence CDC2 Protein Kinase/metabolism Cell Cycle Proteins Chromosome Mapping Cyclin B/metabolism DNA Primers/genetics Fungal Proteins Gene Deletion Genes, Fungal Mitosis/physiology Molecular Sequence Data Mutation Nitrogen/metabolism Nuclear Proteins Phosphorylation Protein Serine-Threonine Kinases/genetics,metabolism Protein-Tyrosine Kinases/genetics,metabolism Schizosaccharomyces/cytology,genetics,metabolism Schizosaccharomyces pombe Proteins Sequence Homology, Amino Acid Tyrosine/metabolism
Chemicals
ATP-Binding Cassette Transporters Cell Cycle Proteins Cyclin B DNA Primers Fungal Proteins Nuclear Proteins Schizosaccharomyces pombe Proteins Tyrosine cdr1 protein, S pombe wee1 protein, S pombe Protein-Tyrosine Kinases Protein Serine-Threonine Kinases CDC2 Protein Kinase Nitrogen
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Kanoh J
Departments of Molecular Biology and Cell Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
Russell P
References (57)
57 references, click to expand
  1. Activation and regulation of the Spc1 stress-activated protein kinase in Schizosaccharomyces pombe.
    Mol Cell Biol. 1996 Jun;16(6):2870-7 PMID: 8649397
  2. The essential mitotic peptidyl-prolyl isomerase Pin1 binds and regulates mitosis-specific phosphoproteins.
    Genes Dev. 1998 Mar 1;12(5):706-20 PMID: 9499405
  3. Periodic changes in phosphorylation of the Xenopus cdc25 phosphatase regulate its activity.
    Mol Biol Cell. 1992 Aug;3(8):927-39 PMID: 1392080
  4. Pyp3 PTPase acts as a mitotic inducer in fission yeast.
    EMBO J. 1992 Dec;11(13):4933-41 PMID: 1464318
  5. Thiamine-repressible expression vectors pREP and pRIP for fission yeast.
    Gene. 1993 Jan 15;123(1):127-30 PMID: 8422996
  6. Phosphorylation and activation of human cdc25-C by cdc2--cyclin B and its involvement in the self-amplification of MPF at mitosis.
    EMBO J. 1993 Jan;12(1):53-63 PMID: 8428594
  7. Negative regulation of the wee1 protein kinase by direct action of the nim1/cdr1 mitotic inducer.
    Cell. 1993 Mar 26;72(6):919-29 PMID: 7681363
  8. Phosphorylation and inactivation of the mitotic inhibitor Wee1 by the nim1/cdr1 kinase.
    Nature. 1993 Jun 24;363(6431):736-8 PMID: 8515817
  9. Nim1 kinase promotes mitosis by inactivating Wee1 tyrosine kinase.
    Nature. 1993 Jun 24;363(6431):738-41 PMID: 8515818
  10. Regulation of progression through the G1 phase of the cell cycle by the rum1+ gene.
    Nature. 1994 Jan 20;367(6460):236-42 PMID: 8121488
  11. Elimination of cdc2 phosphorylation sites in the cdc25 phosphatase blocks initiation of M-phase.
    Mol Biol Cell. 1993 Dec;4(12):1337-50 PMID: 7513216
  12. cdc25 is one of the MPM-2 antigens involved in the activation of maturation-promoting factor.
    Mol Biol Cell. 1994 Feb;5(2):135-45 PMID: 8019000
  13. Isolation of type I and II DNA topoisomerase mutants from fission yeast: single and double mutants show different phenotypes in cell growth and chromatin organization.
    EMBO J. 1984 Aug;3(8):1737-44 PMID: 6090122
  14. cdc25+ functions as an inducer in the mitotic control of fission yeast.
    Cell. 1986 Apr 11;45(1):145-53 PMID: 3955656
  15. Negative regulation of mitosis by wee1+, a gene encoding a protein kinase homolog.
    Cell. 1987 May 22;49(4):559-67 PMID: 3032459
  16. The mitotic inducer nim1+ functions in a regulatory network of protein kinase homologs controlling the initiation of mitosis.
    Cell. 1987 May 22;49(4):569-76 PMID: 3453113
  17. Schizosaccharomyces pombe mutants affected in their division response to starvation.
    J Cell Sci. 1987 Oct;88 ( Pt 3):295-304 PMID: 3448096
  18. Genetic engineering of Schizosaccharomyces pombe: a system for gene disruption and replacement using the ura4 gene as a selectable marker.
    Mol Gen Genet. 1988 Dec;215(1):81-6 PMID: 3241624
  19. Tyrosine phosphorylation of the fission yeast cdc2+ protein kinase regulates entry into mitosis.
    Nature. 1989 Nov 2;342(6245):39-45 PMID: 2682257
  20. Mutation of fission yeast cell cycle control genes abolishes dependence of mitosis on DNA replication.
    Cell. 1990 Feb 23;60(4):665-73 PMID: 2406029
  21. mik1 and wee1 cooperate in the inhibitory tyrosine phosphorylation of cdc2.
    Cell. 1991 Mar 22;64(6):1111-22 PMID: 1706223
  22. Genetic and molecular analysis of cdr1/nim1 in Schizosaccharomyces pombe.
    Genetics. 1991 Feb;127(2):309-18 PMID: 2004705
  23. Phosphorylation at Thr167 is required for Schizosaccharomyces pombe p34cdc2 function.
    EMBO J. 1991 Nov;10(11):3297-309 PMID: 1655416
  24. The wis1 protein kinase is a dosage-dependent regulator of mitosis in Schizosaccharomyces pombe.
    EMBO J. 1991 Dec;10(13):4291-9 PMID: 1756736
  25. p80cdc25 mitotic inducer is the tyrosine phosphatase that activates p34cdc2 kinase in fission yeast.
    EMBO J. 1991 Dec;10(13):4301-9 PMID: 1756737
  26. Control of DNA synthesis genes in fission yeast by the cell-cycle gene cdc10+.
    Nature. 1992 Jan 30;355(6359):449-53 PMID: 1734281
  27. Regulation of the cdc25 protein during the cell cycle in Xenopus extracts.
    Cell. 1992 Jul 10;70(1):139-51 PMID: 1623517
  28. Gin4 of S. cerevisiae is a bud neck protein that interacts with the Cdc28 complex.
    Genes Cells. 1997 Dec;2(12):753-70 PMID: 9544703
  29. Replication checkpoint enforced by kinases Cds1 and Chk1.
    Science. 1998 May 8;280(5365):909-12 PMID: 9572736
  30. Tyrosine phosphorylation of cdc2 is required for the replication checkpoint in Schizosaccharomyces pombe.
    Mol Cell Biol. 1998 Jul;18(7):3782-7 PMID: 9632761
  31. Cell cycle regulation of human WEE1.
    EMBO J. 1995 May 15;14(10):2166-75 PMID: 7774574
  32. Pyp1 and Pyp2 PTPases dephosphorylate an osmosensing MAP kinase controlling cell size at division in fission yeast.
    Genes Dev. 1995 Sep 1;9(17):2117-30 PMID: 7657164
  33. Stockpiling of Cdc25 during a DNA replication checkpoint arrest in Schizosaccharomyces pombe.
    Mol Cell Biol. 1996 Jan;16(1):86-93 PMID: 8524332
  34. Cell-cycle control linked to extracellular environment by MAP kinase pathway in fission yeast.
    Nature. 1995 Dec 14;378(6558):739-43 PMID: 7501024
  35. p25rum1 orders S phase and mitosis by acting as an inhibitor of the p34cdc2 mitotic kinase.
    Cell. 1995 Dec 15;83(6):1001-9 PMID: 8521500
  36. Interaction of Cdc2 and Cdc18 with a fission yeast ORC2-like protein.
    Nature. 1996 Jan 25;379(6563):360-3 PMID: 8552194
  37. Regulation of the human WEE1Hu CDK tyrosine 15-kinase during the cell cycle.
    EMBO J. 1995 May 1;14(9):1878-91 PMID: 7743995
  38. Cell cycle regulation of a Xenopus Wee1-like kinase.
    Mol Biol Cell. 1995 Jan;6(1):119-34 PMID: 7749193
  39. Purification and molecular cloning of Plx1, a Cdc25-regulatory kinase from Xenopus egg extracts.
    Science. 1996 Sep 6;273(5280):1377-80 PMID: 8703070
  40. The role of proteolysis in cell cycle progression in Schizosaccharomyces pombe.
    EMBO J. 1996 Oct 1;15(19):5268-79 PMID: 8895572
  41. Spatial organization of the Nim1-Wee1-Cdc2 mitotic control network in Schizosaccharomyces pombe.
    Mol Biol Cell. 1996 Nov;7(11):1749-58 PMID: 8930897
  42. Roles of Wee1 and Nim1 protein kinases in regulating the switch from mitotic division to sexual development in Schizosaccharomyces pombe.
    Mol Cell Biol. 1997 Jan;17(1):10-7 PMID: 8972180
  43. Cdc2 tyrosine phosphorylation is required for the DNA damage checkpoint in fission yeast.
    Genes Dev. 1997 Feb 15;11(4):504-11 PMID: 9042863
  44. Nik1: a Nim1-like protein kinase of S. cerevisiae interacts with the Cdc28 complex and regulates cell cycle progression.
    Genes Cells. 1996 Oct;1(10):905-21 PMID: 9077450
  45. Nif1, a novel mitotic inhibitor in Schizosaccharomyces pombe.
    EMBO J. 1997 Mar 17;16(6):1342-50 PMID: 9135149
  46. The Mcs4 response regulator coordinately controls the stress-activated Wak1-Wis1-Sty1 MAP kinase pathway and fission yeast cell cycle.
    Genes Dev. 1997 Apr 15;11(8):1008-22 PMID: 9136929
  47. Screening and identification of yeast sequences that cause growth inhibition when overexpressed.
    Mol Gen Genet. 1997 Apr 16;254(3):267-74 PMID: 9150260
  48. Regulation of Schizosaccharomyces pombe Wee1 tyrosine kinase.
    J Biol Chem. 1997 May 16;272(20):13320-5 PMID: 9148953
  49. Discrete roles of the Spc1 kinase and the Atf1 transcription factor in the UV response of Schizosaccharomyces pombe.
    Mol Cell Biol. 1997 Jun;17(6):3356-63 PMID: 9154834
  50. Mcs4 mitotic catastrophe suppressor regulates the fission yeast cell cycle through the Wik1-Wis1-Spc1 kinase cascade.
    Mol Biol Cell. 1997 Mar;8(3):409-19 PMID: 9188094
  51. Control of mitotic events by Nap1 and the Gin4 kinase.
    J Cell Biol. 1997 Jul 14;138(1):119-30 PMID: 9214386
  52. Stress-activated protein kinase pathway in cell cycle control of fission yeast.
    Methods Enzymol. 1997;283:506-20 PMID: 9251044
  53. Cdc25 mitotic inducer targeted by chk1 DNA damage checkpoint kinase.
    Science. 1997 Sep 5;277(5331):1495-7 PMID: 9278510
  54. Multiple modes of activation of the stress-responsive MAP kinase pathway in fission yeast.
    EMBO J. 1997 Oct 15;16(20):6162-70 PMID: 9321395
  55. The mitotic peptidyl-prolyl isomerase, Pin1, interacts with Cdc25 and Plx1.
    EMBO J. 1998 Aug 10;17(5):1315-27 PMID: 9482729
  56. The polo-like kinase Plx1 is required for M phase exit and destruction of mitotic regulators in Xenopus egg extracts.
    EMBO J. 1998 Mar 2;17(5):1328-35 PMID: 9482730
  57. A search for proteins that interact genetically with histone H3 and H4 amino termini uncovers novel regulators of the Swe1 kinase in Saccharomyces cerevisiae.
    Genes Dev. 1996 Jun 1;10(11):1327-40 PMID: 8647431
Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1059-1524
DOI
10.1091/mbc.9.12.3321
Published
1998-12-00
Pages
3321-34
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC25629
Subset
IM
External Links
PubMed source DOI: 10.1091/mbc.9.12.3321 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2