Home LiteratureArticle Details
PMID: 12642613 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Budding yeast PAK kinases regulate mitotic exit by two different mechanisms.

The Journal of cell biology ·Vol. 160 ·No. 6 ·2003-03-17 ·Pages 857-74

Chiroli E, Fraschini R, Beretta A, Tonelli M, Lucchini G, Piatti S

Abstract

We report the characterization of the dominant-negative CLA4t allele of the budding yeast CLA4 gene, encoding a member of the p21-activated kinase (PAK) family of protein kinases, which, together with its homologue STE20, plays an essential role in promoting budding and cytokinesis. Overproduction of the Cla4t protein likely inhibits both endogenous Cla4 and Ste20 and causes a delay in the onset of anaphase that correlates with inactivation of Cdc20/anaphase-promoting complex (APC)-dependent proteolysis of both the cyclinB Clb2 and securin. Although the precise mechanism of APC inhibition by Cla4t remains to be elucidated, our results suggest that Cla4 and Ste20 may regulate the first wave of cyclinB proteolysis mediated by Cdc20/APC, which has been shown to be crucial for activation of the mitotic exit network (MEN). We show that the Cdk1-inhibitory kinase Swe1 is required for the Cla4t-dependent delay in cell cycle progression, suggesting that it might be required to prevent full Cdc20/APC and MEN activation. In addition, inhibition of PAK kinases by Cla4t prevents mitotic exit also by a Swe1-independent mechanism impinging directly on the MEN activator Tem1.

MeSH Terms
Anaphase/physiology Anaphase-Promoting Complex-Cyclosome Cell Cycle Proteins/genetics,metabolism Cells, Cultured Cyclin B/genetics,metabolism Genes, cdc/physiology Intracellular Signaling Peptides and Proteins Ligases/genetics,metabolism MAP Kinase Kinase Kinases Mitosis/genetics Monomeric GTP-Binding Proteins/genetics,metabolism Mutation/genetics Nuclear Proteins/genetics,metabolism Protein Serine-Threonine Kinases/genetics,metabolism Protein-Tyrosine Kinases/genetics Saccharomyces cerevisiae/enzymology,genetics Saccharomyces cerevisiae Proteins/genetics,metabolism Securin Ubiquitin-Protein Ligase Complexes
Chemicals
Cell Cycle Proteins Cyclin B Intracellular Signaling Peptides and Proteins Nuclear Proteins PDS1 protein, S cerevisiae Saccharomyces cerevisiae Proteins Securin TEM1 protein, S cerevisiae Ubiquitin-Protein Ligase Complexes Anaphase-Promoting Complex-Cyclosome SWE1 protein, S cerevisiae Protein-Tyrosine Kinases CLA4 protein, S cerevisiae Protein Serine-Threonine Kinases MAP Kinase Kinase Kinases STE20 protein, S cerevisiae Monomeric GTP-Binding Proteins Ligases
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Chiroli Elena
Dipartimento di Biotecnologie e Bioscienze, Piazza della Scienza 2, 20126 Milano, Italy.
Fraschini Roberta
Beretta Alessia
Tonelli Mariagrazia
Lucchini Giovanna
Piatti Simonetta
References (73)
73 references, click to expand
  1. The surveillance mechanism of the spindle position checkpoint in yeast.
    J Cell Biol. 2001 Apr 2;153(1):159-68 PMID: 11285282
  2. Isolation and characterization of effector-loop mutants of CDC42 in yeast.
    Mol Biol Cell. 2001 May;12(5):1239-55 PMID: 11359919
  3. A new view of the spindle checkpoint.
    J Cell Biol. 2001 Sep 3;154(5):909-11 PMID: 11535614
  4. Men and sin: what's the difference?
    Nat Rev Mol Cell Biol. 2001 Nov;2(11):815-26 PMID: 11715048
  5. Bub3 interaction with Mad2, Mad3 and Cdc20 is mediated by WD40 repeats and does not require intact kinetochores.
    EMBO J. 2001 Dec 3;20(23):6648-59 PMID: 11726501
  6. Regulation of the Bub2/Bfa1 GAP complex by Cdc5 and cell cycle checkpoints.
    Cell. 2001 Nov 30;107(5):655-65 PMID: 11733064
  7. The mitotic spindle checkpoint.
    Curr Biol. 2001 Dec 11;11(24):R1001-4 PMID: 11747833
  8. Pak1 kinase homodimers are autoinhibited in trans and dissociated upon activation by Cdc42 and Rac1.
    Mol Cell. 2002 Jan;9(1):73-83 PMID: 11804587
  9. Separase, polo kinase, the kinetochore protein Slk19, and Spo12 function in a network that controls Cdc14 localization during early anaphase.
    Cell. 2002 Jan 25;108(2):207-20 PMID: 11832211
  10. A Bub2p-dependent spindle checkpoint pathway regulates the Dbf2p kinase in budding yeast.
    EMBO J. 1999 May 4;18(9):2424-34 PMID: 10228157
  11. Sister chromatid separation and chromosome re-duplication are regulated by different mechanisms in response to spindle damage.
    EMBO J. 1999 May 17;18(10):2707-21 PMID: 10329618
  12. Budding yeast Bub2 is localized at spindle pole bodies and activates the mitotic checkpoint via a different pathway from Mad2.
    J Cell Biol. 1999 May 31;145(5):979-91 PMID: 10352016
  13. Epitope tagging of yeast genes using a PCR-based strategy: more tags and improved practical routines.
    Yeast. 1999 Jul;15(10B):963-72 PMID: 10407276
  14. Pds1 and Esp1 control both anaphase and mitotic exit in normal cells and after DNA damage.
    Genes Dev. 1999 Aug 1;13(15):1936-49 PMID: 10444592
  15. Pds1p of budding yeast has dual roles: inhibition of anaphase initiation and regulation of mitotic exit.
    Genes Dev. 1999 Aug 1;13(15):1950-9 PMID: 10444593
  16. Whose end is destruction: cell division and the anaphase-promoting complex.
    Genes Dev. 1999 Aug 15;13(16):2039-58 PMID: 10465783
  17. The morphogenesis checkpoint in Saccharomyces cerevisiae: cell cycle control of Swe1p degradation by Hsl1p and Hsl7p.
    Mol Cell Biol. 1999 Oct;19(10):6929-39 PMID: 10490630
  18. Cdc20 is essential for the cyclosome-mediated proteolysis of both Pds1 and Clb2 during M phase in budding yeast.
    Curr Biol. 1998 Feb 12;8(4):231-4 PMID: 9501986
  19. Destruction of the CDC28/CLB mitotic kinase is not required for the metaphase to anaphase transition in budding yeast.
    EMBO J. 1993 May;12(5):1969-78 PMID: 8491189
  20. The Schizosaccharomyces pombe cdc14 gene is required for septum formation and can also inhibit nuclear division.
    Mol Biol Cell. 1993 May;4(5):531-9 PMID: 8334307
  21. 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
  22. Mitotic checkpoint genes in budding yeast and the dependence of mitosis on DNA replication and repair.
    Genes Dev. 1994 Mar 15;8(6):652-65 PMID: 7926756
  23. Isolation of a CDC25 family gene, MSI2/LTE1, as a multicopy suppressor of ira1.
    Yeast. 1994 Apr;10(4):451-61 PMID: 7941731
  24. A cell cycle checkpoint monitors cell morphogenesis in budding yeast.
    J Cell Biol. 1995 May;129(3):739-49 PMID: 7730408
  25. New heterologous modules for classical or PCR-based gene disruptions in Saccharomyces cerevisiae.
    Yeast. 1994 Dec;10(13):1793-808 PMID: 7747518
  26. Ste20-like protein kinases are required for normal localization of cell growth and for cytokinesis in budding yeast.
    Genes Dev. 1995 Aug 1;9(15):1817-30 PMID: 7649470
  27. The septins: roles in cytokinesis and other processes.
    Curr Opin Cell Biol. 1996 Feb;8(1):106-19 PMID: 8791410
  28. Septins may form a ubiquitous family of cytoskeletal filaments.
    J Cell Biol. 1996 Sep;134(6):1345-8 PMID: 8830765
  29. PAK-family kinases regulate cell and actin polarization throughout the cell cycle of Saccharomyces cerevisiae.
    J Cell Biol. 1999 Nov 15;147(4):845-56 PMID: 10562285
  30. APC(Cdc20) promotes exit from mitosis by destroying the anaphase inhibitor Pds1 and cyclin Clb5.
    Nature. 1999 Nov 11;402(6758):203-7 PMID: 10647015
  31. Roles of Hof1p, Bni1p, Bnr1p, and myo1p in cytokinesis in Saccharomyces cerevisiae.
    Mol Biol Cell. 2000 Feb;11(2):593-611 PMID: 10679017
  32. Cell-cycle checkpoints that ensure coordination between nuclear and cytoplasmic events in Saccharomyces cerevisiae.
    Curr Opin Genet Dev. 2000 Feb;10(1):47-53 PMID: 10679396
  33. Two different modes of cyclin clb2 proteolysis during mitosis in Saccharomyces cerevisiae.
    FEBS Lett. 2000 Feb 25;468(2-3):142-8 PMID: 10692575
  34. A checkpoint that monitors cytokinesis in Schizosaccharomyces pombe.
    J Cell Sci. 2000 Apr;113 ( Pt 7):1223-30 PMID: 10704373
  35. Regulation of the Bfa1p-Bub2p complex at spindle pole bodies by the cell cycle phosphatase Cdc14p.
    J Cell Biol. 2002 Apr 29;157(3):367-79 PMID: 11970961
  36. The anaphase-promoting complex: proteolysis in mitosis and beyond.
    Mol Cell. 2002 May;9(5):931-43 PMID: 12049731
  37. Mitotic exit network controls the localization of Cdc14 to the spindle pole body in Saccharomyces cerevisiae.
    Curr Biol. 2002 Jun 4;12(11):944-50 PMID: 12062061
  38. MEN, destruction and separation: mechanistic links between mitotic exit and cytokinesis in budding yeast.
    Bioessays. 2002 Jul;24(7):659-66 PMID: 12111726
  39. APC-dependent proteolysis of the mitotic cyclin Clb2 is essential for mitotic exit.
    Nature. 2002 Aug 1;418(6897):556-62 PMID: 12152084
  40. Mitotic exit: the Cdc14 double cross.
    Curr Biol. 2002 Jul 23;12(14):R482-84 PMID: 12176346
  41. A role for cell polarity proteins in mitotic exit.
    EMBO J. 2002 Sep 16;21(18):4851-62 PMID: 12234925
  42. The spindle checkpoint: structural insights into dynamic signalling.
    Nat Rev Mol Cell Biol. 2002 Oct;3(10):731-41 PMID: 12360190
  43. Control of Lte1 localization by cell polarity determinants and Cdc14.
    Curr Biol. 2002 Dec 23;12(24):2098-110 PMID: 12498684
  44. Diverse effects of beta-tubulin mutations on microtubule formation and function.
    J Cell Biol. 1988 Jun;106(6):1997-2010 PMID: 3290223
  45. Checkpoints: controls that ensure the order of cell cycle events.
    Science. 1989 Nov 3;246(4930):629-34 PMID: 2683079
  46. CDC42 and CDC43, two additional genes involved in budding and the establishment of cell polarity in the yeast Saccharomyces cerevisiae.
    J Cell Biol. 1990 Jul;111(1):131-42 PMID: 2195038
  47. Getting started with yeast.
    Methods Enzymol. 1991;194:3-21 PMID: 2005794
  48. The role of CDC28 and cyclins during mitosis in the budding yeast S. cerevisiae.
    Cell. 1991 Apr 5;65(1):145-61 PMID: 1849457
  49. Characterization of four B-type cyclin genes of the budding yeast Saccharomyces cerevisiae.
    Mol Biol Cell. 1992 Jul;3(7):805-18 PMID: 1387566
  50. Spindle pole body separation in Saccharomyces cerevisiae requires dephosphorylation of the tyrosine 19 residue of Cdc28.
    Mol Cell Biol. 1996 Nov;16(11):6385-97 PMID: 8887667
  51. Cla4p, a Saccharomyces cerevisiae Cdc42p-activated kinase involved in cytokinesis, is activated at mitosis.
    Mol Cell Biol. 1997 Sep;17(9):5067-76 PMID: 9271384
  52. CDC20 and CDH1: a family of substrate-specific activators of APC-dependent proteolysis.
    Science. 1997 Oct 17;278(5337):460-3 PMID: 9334304
  53. The Cdc42 GTPase-associated proteins Gic1 and Gic2 are required for polarized cell growth in Saccharomyces cerevisiae.
    Genes Dev. 1997 Nov 15;11(22):2958-71 PMID: 9367979
  54. Novel Cdc42-binding proteins Gic1 and Gic2 control cell polarity in yeast.
    Genes Dev. 1997 Nov 15;11(22):2972-82 PMID: 9367980
  55. Budding yeast Cdc20: a target of the spindle checkpoint.
    Science. 1998 Feb 13;279(5353):1041-4 PMID: 9461437
  56. Involvement of an actomyosin contractile ring in Saccharomyces cerevisiae cytokinesis.
    J Cell Biol. 1998 Sep 7;142(5):1301-12 PMID: 9732290
  57. The phosphatase Cdc14 triggers mitotic exit by reversal of Cdk-dependent phosphorylation.
    Mol Cell. 1998 Dec;2(6):709-18 PMID: 9885559
  58. Cytokinesis in eukaryotes: a mechanistic comparison.
    Curr Opin Cell Biol. 1999 Feb;11(1):68-80 PMID: 10047527
  59. Cdc42: An essential Rho-type GTPase controlling eukaryotic cell polarity.
    Microbiol Mol Biol Rev. 1999 Mar;63(1):54-105 PMID: 10066831
  60. Bifurcation of the mitotic checkpoint pathway in budding yeast.
    Proc Natl Acad Sci U S A. 1999 Apr 27;96(9):4989-94 PMID: 10220406
  61. The role of the sid1p kinase and cdc14p in regulating the onset of cytokinesis in fission yeast.
    EMBO J. 2000 Apr 17;19(8):1803-15 PMID: 10775265
  62. Septin-dependent assembly of a cell cycle-regulatory module in Saccharomyces cerevisiae.
    Mol Cell Biol. 2000 Jun;20(11):4049-61 PMID: 10805747
  63. Cdc14 activates cdc15 to promote mitotic exit in budding yeast.
    Curr Biol. 2000 May 18;10(10):615-8 PMID: 10837230
  64. Cdc28 activates exit from mitosis in budding yeast.
    J Cell Biol. 2000 Jun 26;149(7):1361-76 PMID: 10871278
  65. Phosphorylation by Cdc28 activates the Cdc20-dependent activity of the anaphase-promoting complex.
    J Cell Biol. 2000 Jun 26;149(7):1377-90 PMID: 10871279
  66. Exit from mitosis in budding yeast: biphasic inactivation of the Cdc28-Clb2 mitotic kinase and the role of Cdc20.
    Mol Cell. 2000 Mar;5(3):501-11 PMID: 10882135
  67. A mechanism for coupling exit from mitosis to partitioning of the nucleus.
    Cell. 2000 Jul 7;102(1):21-31 PMID: 10929710
  68. The Bub2p spindle checkpoint links nuclear migration with mitotic exit.
    Mol Cell. 2000 Jul;6(1):1-10 PMID: 10949022
  69. Exit from mitosis: spindle pole power.
    Cell. 2000 Aug 4;102(3):267-70 PMID: 10975516
  70. Chemical genetic analysis of the budding-yeast p21-activated kinase Cla4p.
    Nat Cell Biol. 2000 Oct;2(10):677-85 PMID: 11025657
  71. The phosphotyrosyl phosphatase activator, Ncs1p (Rrd1p), functions with Cla4p to regulate the G(2)/M transition in Saccharomyces cerevisiae.
    Mol Cell Biol. 2001 Jan;21(2):488-500 PMID: 11134337
  72. Mitotic checkpoints: from yeast to cancer.
    Curr Opin Genet Dev. 2001 Feb;11(1):83-90 PMID: 11163156
  73. Timing is everything: regulation of mitotic exit and cytokinesis by the MEN and SIN.
    Trends Cell Biol. 2001 Feb;11(2):89-95 PMID: 11166217
Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.200209097
Published
2003-03-17
Pages
857-74
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2173773
Subset
IM
External Links
PubMed source DOI: 10.1083/jcb.200209097 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