Home LiteratureArticle Details
PMID: 8573790 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Drosophila Wee1 kinase rescues fission yeast from mitotic catastrophe and phosphorylates Drosophila Cdc2 in vitro.

Molecular biology of the cell ·Vol. 6 ·No. 10 ·1995-10-00 ·Pages 1333-47

Campbell SD, Sprenger F, Edgar BA, O'Farrell PH

Abstract

Cdc2 kinase activity is required for triggering entry into mitosis in all known eukaryotes. Elaborate mechanisms have evolved for regulating Cdc2 activity so that mitosis occurs in a timely manner, when preparations for its execution are complete. In Schizosaccharomyces pombe, Wee1 and a related Mik1 kinase are Cdc2-inhibitory kinases that are required for preventing premature activation of the mitotic program. To identify Cdc2-inhibitory kinases in Drosophila, we screened for cDNA clones that rescue S. pombe wee1- mik1- mutants from lethal mitotic catastrophe. One of the genes identified in this screen, Drosophila wee1 (Dwee1), encodes a new Wee1 homologue. Dwee1 kinase is closely related to human and Xenopus Wee1 homologues, and can inhibit Cdc2 activity by phosphorylating a critical tyrosine residue. Dwee1 mRNA is maternally provided to embryos, and is zygotically expressed during the postblastoderm divisions of embryogenesis. Expression remains high in the proliferating cells of the central nervous system well after cells in the rest of the embryo have ceased dividing. The loss of zygotically expressed Dwee1 does not lead to mitotic catastrophe during postblastoderm cycles 14 to 16. This result may indicate that maternally provided Dwee1 is sufficient for regulating Cdc2 during embryogenesis, or it may reflect the presence of a redundant Cdc2 inhibitory kinase, as in fission yeast.

MeSH Terms
Amino Acid Sequence Animals Base Sequence CDC2 Protein Kinase/antagonists & inhibitors,metabolism Cell Cycle Proteins Chromosome Mapping Cloning, Molecular Drosophila/embryology,enzymology,genetics Gene Expression Regulation, Developmental Gene Expression Regulation, Enzymologic Genes Genetic Complementation Test Humans Mitosis/physiology Molecular Sequence Data Nervous System/enzymology Nuclear Proteins Phosphorylation Protein-Tyrosine Kinases/analysis,metabolism,physiology RNA, Messenger/analysis Schizosaccharomyces/genetics,physiology Schizosaccharomyces pombe Proteins Sequence Analysis, DNA Sequence Homology, Amino Acid Tyrosine/metabolism
Chemicals
Cell Cycle Proteins Nuclear Proteins RNA, Messenger Schizosaccharomyces pombe Proteins Tyrosine wee1 protein, S pombe Protein-Tyrosine Kinases WEE1 protein, human CDC2 Protein Kinase
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Campbell S D
Department of Biochemistry and Biophysics, University of California, San Francisco 94143-0448, USA.
Sprenger F
Edgar B A
O'Farrell P H
References (62)
62 references, click to expand
  1. 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
  2. Negative regulation of mitosis by wee1+, a gene encoding a protein kinase homolog.
    Cell. 1987 May 22;49(4):559-67 PMID: 3032459
  3. Genetic and molecular analysis of cdr1/nim1 in Schizosaccharomyces pombe.
    Genetics. 1991 Feb;127(2):309-18 PMID: 2004705
  4. The roles of Drosophila cyclins A and B in mitotic control.
    Cell. 1990 May 4;61(3):535-47 PMID: 2139805
  5. The Drosophila cdc25 homolog twine is required for meiosis.
    Development. 1992 Oct;116(2):405-16 PMID: 1286615
  6. Genetic control of cell size at cell division in yeast.
    Nature. 1975 Aug 14;256(5518):547-51 PMID: 1165770
  7. Isolation of cell size mutants of a fission yeast by a new selective method: characterization of mutants and implications for division control mechanisms.
    J Bacteriol. 1981 May;146(2):746-54 PMID: 7217015
  8. Human wee1 maintains mitotic timing by protecting the nucleus from cytoplasmically activated Cdc2 kinase.
    Cell. 1993 Aug 13;74(3):463-74 PMID: 8348613
  9. Phosphorylation and inactivation of the mitotic inhibitor Wee1 by the nim1/cdr1 kinase.
    Nature. 1993 Jun 24;363(6431):736-8 PMID: 8515817
  10. Negative regulation of mitosis by two functionally overlapping PTPases in fission yeast.
    EMBO J. 1992 Dec;11(13):4943-52 PMID: 1464319
  11. Coupling of mitosis to the completion of S phase in Xenopus occurs via modulation of the tyrosine kinase that phosphorylates p34cdc2.
    Cell. 1992 Feb 21;68(4):787-97 PMID: 1531451
  12. Two distinct mechanisms localise cyclin B transcripts in syncytial Drosophila embryos.
    Development. 1990 Dec;110(4):1249-61 PMID: 2151612
  13. Dephosphorylation and activation of Xenopus p34cdc2 protein kinase during the cell cycle.
    Nature. 1989 Jun 22;339(6226):626-9 PMID: 2543932
  14. Properties of Saccharomyces cerevisiae wee1 and its differential regulation of p34CDC28 in response to G1 and G2 cyclins.
    EMBO J. 1993 Sep;12(9):3417-26 PMID: 8253069
  15. The role of cyclin synthesis and degradation in the control of maturation promoting factor activity.
    Nature. 1989 May 25;339(6222):280-6 PMID: 2566918
  16. 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
  17. Control of the timing of cell division in fission yeast. Cell size mutants reveal a second control pathway.
    Exp Cell Res. 1978 Sep;115(2):317-29 PMID: 689088
  18. Wee1(+)-like gene in human cells.
    Nature. 1991 Sep 5;353(6339):80-3 PMID: 1840647
  19. Genetic analysis of the Drosophila cdc2 homolog.
    Development. 1993 Jan;117(1):219-32 PMID: 8223248
  20. Tyrosine phosphorylation of the fission yeast cdc2+ protein kinase regulates entry into mitosis.
    Nature. 1989 Nov 2;342(6245):39-45 PMID: 2682257
  21. Accurate and efficient RNA polymerase II transcription with a soluble nuclear fraction derived from Drosophila embryos.
    Proc Natl Acad Sci U S A. 1991 Feb 1;88(3):1024-8 PMID: 1992453
  22. Dual functions of CDC6: a yeast protein required for DNA replication also inhibits nuclear division.
    EMBO J. 1992 Jun;11(6):2167-76 PMID: 1600944
  23. Genetic control of cell division patterns in the Drosophila embryo.
    Cell. 1989 Apr 7;57(1):177-87 PMID: 2702688
  24. Toward a molecular genetic analysis of spermatogenesis in Drosophila melanogaster: characterization of male-sterile mutants generated by single P element mutagenesis.
    Genetics. 1993 Oct;135(2):489-505 PMID: 8244010
  25. mik1 and wee1 cooperate in the inhibitory tyrosine phosphorylation of cdc2.
    Cell. 1991 Mar 22;64(6):1111-22 PMID: 1706223
  26. Role of phosphorylation in p34cdc2 activation: identification of an activating kinase.
    Mol Biol Cell. 1992 Jan;3(1):13-27 PMID: 1532335
  27. Functional cDNA libraries from Drosophila embryos.
    J Mol Biol. 1988 Sep 20;203(2):425-37 PMID: 3199441
  28. Protein kinase catalytic domain sequence database: identification of conserved features of primary structure and classification of family members.
    Methods Enzymol. 1991;200:38-62 PMID: 1956325
  29. The three postblastoderm cell cycles of Drosophila embryogenesis are regulated in G2 by string.
    Cell. 1990 Aug 10;62(3):469-80 PMID: 2199063
  30. Cell cycle regulation of a Xenopus Wee1-like kinase.
    Mol Biol Cell. 1995 Jan;6(1):119-34 PMID: 7749193
  31. nmt1 of fission yeast. A highly transcribed gene completely repressed by thiamine.
    J Biol Chem. 1990 Jul 5;265(19):10857-64 PMID: 2358444
  32. Regulation of the human WEE1Hu CDK tyrosine 15-kinase during the cell cycle.
    EMBO J. 1995 May 1;14(9):1878-91 PMID: 7743995
  33. The regulation of the cell cycle during Drosophila embryogenesis: the transition to polyteny.
    Development. 1991 Aug;112(4):997-1008 PMID: 1935703
  34. Unidirectional digestion with exonuclease III creates targeted breakpoints for DNA sequencing.
    Gene. 1984 Jun;28(3):351-9 PMID: 6235151
  35. Nim1 kinase promotes mitosis by inactivating Wee1 tyrosine kinase.
    Nature. 1993 Jun 24;363(6431):738-41 PMID: 8515818
  36. Identification of a Xenopus cDNA that prevents mitotic catastrophe in the fission yeast Schizosaccharomyces pombe.
    Gene. 1994 Jul 22;145(1):155-6 PMID: 8045419
  37. Two distinct mechanisms for negative regulation of the Wee1 protein kinase.
    EMBO J. 1993 Sep;12(9):3427-36 PMID: 7504624
  38. 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
  39. Periodic changes in phosphorylation of the Xenopus cdc25 phosphatase regulate its activity.
    Mol Biol Cell. 1992 Aug;3(8):927-39 PMID: 1392080
  40. Cell cycle tyrosine phosphorylation of p34cdc2 and a microtubule-associated protein kinase homolog in Xenopus oocytes and eggs.
    Mol Cell Biol. 1991 Apr;11(4):1965-71 PMID: 2005892
  41. Cyclin A potentiates maturation-promoting factor activation in the early Xenopus embryo via inhibition of the tyrosine kinase that phosphorylates cdc2.
    J Cell Biol. 1992 Sep;118(5):1109-20 PMID: 1387401
  42. Chromosomal walking and jumping to isolate DNA from the Ace and rosy loci and the bithorax complex in Drosophila melanogaster.
    J Mol Biol. 1983 Jul 25;168(1):17-33 PMID: 6410077
  43. Studies of nuclear and cytoplasmic behaviour during the five mitotic cycles that precede gastrulation in Drosophila embryogenesis.
    J Cell Sci. 1983 May;61:31-70 PMID: 6411748
  44. Cell cycle control: many ways to skin a cat.
    Trends Cell Biol. 1992 Jun;2(6):159-63 PMID: 14731984
  45. Regulation of mitosis by cyclic accumulation of p80cdc25 mitotic inducer in fission yeast.
    Nature. 1990 Apr 5;344(6266):549-52 PMID: 2320127
  46. Analysis of subtelomeric heterochromatin in the Drosophila minichromosome Dp1187 by single P element insertional mutagenesis.
    Genetics. 1992 Nov;132(3):737-53 PMID: 1334894
  47. Mitosis in transition.
    Cell. 1994 Nov 18;79(4):563-71 PMID: 7954823
  48. cdc25 is a specific tyrosine phosphatase that directly activates p34cdc2.
    Cell. 1991 Oct 4;67(1):197-211 PMID: 1913817
  49. Genetic analysis of the adenosine3 (Gart) region of the second chromosome of Drosophila melanogaster.
    Genetics. 1990 Apr;124(4):889-97 PMID: 2108904
  50. Thiamine-repressible expression vectors pREP and pRIP for fission yeast.
    Gene. 1993 Jan 15;123(1):127-30 PMID: 8422996
  51. Cyclin activation of p34cdc2.
    Cell. 1990 Nov 30;63(5):1013-24 PMID: 2147872
  52. Regulatory genes controlling mitosis in the fission yeast Schizosaccharomyces pombe.
    Genetics. 1980 Nov;96(3):627-37 PMID: 7262540
  53. Translation of cyclin mRNA is necessary for extracts of activated xenopus eggs to enter mitosis.
    Cell. 1989 Mar 24;56(6):947-56 PMID: 2564315
  54. Distinct molecular mechanism regulate cell cycle timing at successive stages of Drosophila embryogenesis.
    Genes Dev. 1994 Feb 15;8(4):440-52 PMID: 7510257
  55. Cell cycle regulation of human WEE1.
    EMBO J. 1995 May 15;14(10):2166-75 PMID: 7774574
  56. Fission yeast p13 blocks mitotic activation and tyrosine dephosphorylation of the Xenopus cdc2 protein kinase.
    Cell. 1989 Jul 14;58(1):181-91 PMID: 2473838
  57. Epistatic gene interactions in the control of division in fission yeast.
    Nature. 1979 May 31;279(5712):428-30 PMID: 16068179
  58. Discrete sequence elements control posterior pole accumulation and translational repression of maternal cyclin B RNA in Drosophila.
    EMBO J. 1993 Mar;12(3):1219-27 PMID: 8458334
  59. The cdc25 protein controls tyrosine dephosphorylation of the cdc2 protein in a cell-free system.
    Cell. 1991 Mar 8;64(5):903-14 PMID: 1825803
  60. Ordering S phase and M phase in the cell cycle.
    Cell. 1994 Nov 18;79(4):547-50 PMID: 7954820
  61. cdc25+ functions as an inducer in the mitotic control of fission yeast.
    Cell. 1986 Apr 11;45(1):145-53 PMID: 3955656
  62. twine, a cdc25 homolog that functions in the male and female germline of Drosophila.
    Cell. 1992 Jun 12;69(6):977-88 PMID: 1606618
Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1059-1524
DOI
10.1091/mbc.6.10.1333
Published
1995-10-00
Pages
1333-47
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC301291
Subset
IM
Grants
NIGMS NIH HHS · R01 GM037193 · United States
NIGMS NIH HHS · R01-GM57193 · United States
Databases
GENBANK
U17223
External Links
PubMed source DOI: 10.1091/mbc.6.10.1333 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: product@genelibs.com

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