Home LiteratureArticle Details
PMID: 21119008 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

The Zds proteins control entry into mitosis and target protein phosphatase 2A to the Cdc25 phosphatase.

Molecular biology of the cell ·Vol. 22 ·No. 1 ·2011-01-01 ·Pages 20-32

Wicky S, Tjandra H, Schieltz D, Yates J, Kellogg DR

Abstract

The Wee1 kinase restrains entry into mitosis by phosphorylating and inhibiting cyclin-dependent kinase 1 (Cdk1). The Cdc25 phosphatase promotes entry into mitosis by removing Cdk1 inhibitory phosphorylation. Experiments in diverse systems have established that Wee1 and Cdc25 are regulated by protein phosphatase 2A (PP2A), but a full understanding of the function and regulation of PP2A in entry into mitosis has remained elusive. In budding yeast, entry into mitosis is controlled by a specific form of PP2A that is associated with the Cdc55 regulatory subunit (PP2A(Cdc55)). We show here that related proteins called Zds1 and Zds2 form a tight stoichiometric complex with PP2A(Cdc55) and target its activity to Cdc25 but not to Wee1. Conditional inactivation of the Zds proteins revealed that their function is required primarily at entry into mitosis. In addition, Zds1 undergoes cell cycle-dependent changes in phosphorylation. Together, these observations define a role for the Zds proteins in controlling specific functions of PP2A(Cdc55) and suggest that upstream signals that regulate PP2A(Cdc55) may play an important role in controlling entry into mitosis.

MeSH Terms
Blotting, Western CDC2 Protein Kinase/genetics,metabolism Cell Cycle Cell Cycle Proteins/genetics,metabolism Fungal Proteins/genetics,metabolism Genes, cdc Mass Spectrometry Mitosis Phosphorylation Protein Phosphatase 2/genetics,metabolism Signal Transduction Yeasts/genetics,metabolism cdc25 Phosphatases/genetics,metabolism
Chemicals
Cell Cycle Proteins Fungal Proteins CDC2 Protein Kinase Protein Phosphatase 2 cdc25 Phosphatases
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Wicky Sidonie
Department of Molecular, Cell, and Developmental Biology, Univ. of California, Santa Cruz, CA 95064, USA.
Tjandra Hendri
Schieltz David
Yates John
Kellogg Douglas R
References (82)
82 references, click to expand
  1. Hsl7 localizes to a septin ring and serves as an adapter in a regulatory pathway that relieves tyrosine phosphorylation of Cdc28 protein kinase in Saccharomyces cerevisiae.
    Mol Cell Biol. 1999 Oct;19(10):7123-37 PMID: 10490648
  2. Cdc25A protein phosphatase: a therapeutic target for liver cancer therapies.
    Anticancer Agents Med Chem. 2008 Dec;8(8):863-71 PMID: 19075569
  3. Phosphorylation and activation of the Xenopus Cdc25 phosphatase in the absence of Cdc2 and Cdk2 kinase activity.
    Mol Biol Cell. 1995 Feb;6(2):215-26 PMID: 7787247
  4. Control of cell size at division in fission yeast by a growth-modulated size control over nuclear division.
    Exp Cell Res. 1977 Jul;107(2):377-86 PMID: 872891
  5. Toward a comprehensive atlas of the physical interactome of Saccharomyces cerevisiae.
    Mol Cell Proteomics. 2007 Mar;6(3):439-50 PMID: 17200106
  6. Protein identification at the low femtomole level from silver-stained gels using a new fritless electrospray interface for liquid chromatography-microspray and nanospray mass spectrometry.
    Anal Biochem. 1998 Oct 1;263(1):93-101 PMID: 9750149
  7. Cdk1 coordinates cell-surface growth with the cell cycle.
    Nat Cell Biol. 2007 May;9(5):506-15 PMID: 17417630
  8. The septins function in G1 pathways that influence the pattern of cell growth in budding yeast.
    PLoS One. 2008 Apr 23;3(4):e2022 PMID: 18431499
  9. Dephosphorylation of cdc25-C by a type-2A protein phosphatase: specific regulation during the cell cycle in Xenopus egg extracts.
    Mol Biol Cell. 1993 Apr;4(4):397-411 PMID: 8389619
  10. Kinases that control the cell cycle in response to DNA damage: Chk1, Chk2, and MK2.
    Curr Opin Cell Biol. 2009 Apr;21(2):245-55 PMID: 19230643
  11. 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
  12. Purification of a multiprotein complex containing centrosomal proteins from the Drosophila embryo by chromatography with low-affinity polyclonal antibodies.
    Mol Biol Cell. 1992 Jan;3(1):1-11 PMID: 1372522
  13. Immunofluorescence methods for yeast.
    Methods Enzymol. 1991;194:565-602 PMID: 2005809
  14. Downregulation of PP2A(Cdc55) phosphatase by separase initiates mitotic exit in budding yeast.
    Cell. 2006 May 19;125(4):719-32 PMID: 16713564
  15. 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
  16. Separase cooperates with Zds1 and Zds2 to activate Cdc14 phosphatase in early anaphase.
    J Cell Biol. 2008 Sep 8;182(5):873-83 PMID: 18762578
  17. Quantitative reconstitution of mitotic CDK1 activation in somatic cell extracts.
    Mol Cell. 2010 Mar 26;37(6):753-67 PMID: 20347419
  18. Localization of Saccharomyces cerevisiae protein phosphatase 2A subunits throughout mitotic cell cycle.
    Mol Biol Cell. 2002 Oct;13(10):3477-92 PMID: 12388751
  19. Conservation of mechanisms controlling entry into mitosis: budding yeast wee1 delays entry into mitosis and is required for cell size control.
    Curr Biol. 2003 Feb 18;13(4):264-75 PMID: 12593792
  20. 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
  21. Additional modules for versatile and economical PCR-based gene deletion and modification in Saccharomyces cerevisiae.
    Yeast. 1998 Jul;14(10):953-61 PMID: 9717241
  22. Mechanisms that help the yeast cell cycle clock tick: G2 cyclins transcriptionally activate G2 cyclins and repress G1 cyclins.
    Cell. 1993 Sep 24;74(6):993-1007 PMID: 8402888
  23. Septin-dependent assembly of a cell cycle-regulatory module in Saccharomyces cerevisiae.
    Mol Cell Biol. 2000 Jun;20(11):4049-61 PMID: 10805747
  24. The role of Saccharomyces cerevisiae type 2A phosphatase in the actin cytoskeleton and in entry into mitosis.
    EMBO J. 1995 Jun 15;14(12):2745-59 PMID: 7796803
  25. Conservation of mitotic controls in fission and budding yeasts.
    Cell. 1989 Apr 21;57(2):295-303 PMID: 2649252
  26. An approach to correlate tandem mass spectral data of peptides with amino acid sequences in a protein database.
    J Am Soc Mass Spectrom. 1994 Nov;5(11):976-89 PMID: 24226387
  27. The role of CDC28 and cyclins during mitosis in the budding yeast S. cerevisiae.
    Cell. 1991 Apr 5;65(1):145-61 PMID: 1849457
  28. Regulated activity of PP2A-B55 delta is crucial for controlling entry into and exit from mitosis in Xenopus egg extracts.
    EMBO J. 2009 Sep 16;28(18):2777-85 PMID: 19696736
  29. Ultrasensitivity in biochemical systems controlled by covalent modification. Interplay between zero-order and multistep effects.
    J Biol Chem. 1984 Dec 10;259(23):14441-7 PMID: 6501300
  30. Two distinct mechanisms for negative regulation of the Wee1 protein kinase.
    EMBO J. 1993 Sep;12(9):3427-36 PMID: 7504624
  31. Regulation of the cdc25 protein during the cell cycle in Xenopus extracts.
    Cell. 1992 Jul 10;70(1):139-51 PMID: 1623517
  32. The elm1 kinase functions in a mitotic signaling network in budding yeast.
    Mol Cell Biol. 1999 Dec;19(12):7983-94 PMID: 10567524
  33. 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
  34. Periodic changes in phosphorylation of the Xenopus cdc25 phosphatase regulate its activity.
    Mol Biol Cell. 1992 Aug;3(8):927-39 PMID: 1392080
  35. A MAP kinase-dependent actin checkpoint ensures proper spindle orientation in fission yeast.
    Nature. 2001 Jul 19;412(6844):352-5 PMID: 11460168
  36. Mitotic phosphatases: no longer silent partners.
    Curr Opin Cell Biol. 2006 Dec;18(6):623-31 PMID: 17030123
  37. The role of actin in spindle orientation changes during the Saccharomyces cerevisiae cell cycle.
    J Cell Biol. 1999 Sep 6;146(5):1019-32 PMID: 10477756
  38. Genetic control of the cell division cycle in the fission yeast Schizosaccharomyces pombe.
    Mol Gen Genet. 1976 Jul 23;146(2):167-78 PMID: 958201
  39. Genetic control of cell size at cell division in yeast.
    Nature. 1975 Aug 14;256(5518):547-51 PMID: 1165770
  40. Cell cycle regulation of a Xenopus Wee1-like kinase.
    Mol Biol Cell. 1995 Jan;6(1):119-34 PMID: 7749193
  41. Tripping the switch fantastic: how a protein kinase cascade can convert graded inputs into switch-like outputs.
    Trends Biochem Sci. 1996 Dec;21(12):460-6 PMID: 9009826
  42. The septins are required for the mitosis-specific activation of the Gin4 kinase.
    J Cell Biol. 1998 Nov 2;143(3):709-17 PMID: 9813092
  43. Processing of adenovirus 2-induced proteins.
    J Virol. 1973 Aug;12(2):241-52 PMID: 4747985
  44. Concerted mechanism of Swe1/Wee1 regulation by multiple kinases in budding yeast.
    EMBO J. 2005 Jun 15;24(12):2194-204 PMID: 15920482
  45. Femtomole sequencing of proteins from polyacrylamide gels by nano-electrospray mass spectrometry.
    Nature. 1996 Feb 1;379(6564):466-9 PMID: 8559255
  46. Protein phosphatase 2A: a highly regulated family of serine/threonine phosphatases implicated in cell growth and signalling.
    Biochem J. 2001 Feb 1;353(Pt 3):417-39 PMID: 11171037
  47. Functional organization of the yeast proteome by systematic analysis of protein complexes.
    Nature. 2002 Jan 10;415(6868):141-7 PMID: 11805826
  48. Yeast casein kinase I homologues: an essential gene pair.
    Proc Natl Acad Sci U S A. 1992 Jan 1;89(1):28-32 PMID: 1729698
  49. Casein kinase I-like protein kinases encoded by YCK1 and YCK2 are required for yeast morphogenesis.
    Mol Cell Biol. 1993 May;13(5):2870-81 PMID: 8474447
  50. An amplified sensitivity arising from covalent modification in biological systems.
    Proc Natl Acad Sci U S A. 1981 Nov;78(11):6840-4 PMID: 6947258
  51. Zds2p regulates Swe1p-dependent polarized cell growth in Saccharomyces cerevisiae via a novel Cdc55p interaction domain.
    Mol Biol Cell. 2010 Dec;21(24):4373-86 PMID: 20980617
  52. ZDS1 and ZDS2, genes whose products may regulate Cdc42p in Saccharomyces cerevisiae.
    Mol Cell Biol. 1996 Oct;16(10):5264-75 PMID: 8816439
  53. Phosphorylation-independent inhibition of Cdc28p by the tyrosine kinase Swe1p in the morphogenesis checkpoint.
    Mol Cell Biol. 1999 Sep;19(9):5981-90 PMID: 10454545
  54. The M phase kinase Greatwall (Gwl) promotes inactivation of PP2A/B55delta, a phosphatase directed against CDK phosphosites.
    Mol Biol Cell. 2009 Nov;20(22):4777-89 PMID: 19793917
  55. Yeast protein serine/threonine phosphatases: multiple roles and diverse regulation.
    Yeast. 1996 Dec;12(16):1647-75 PMID: 9123967
  56. Mutations in the homologous ZDS1 and ZDS2 genes affect cell cycle progression.
    Mol Cell Biol. 1996 Oct;16(10):5254-63 PMID: 8816438
  57. A cell cycle checkpoint monitors cell morphogenesis in budding yeast.
    J Cell Biol. 1995 May;129(3):739-49 PMID: 7730408
  58. Cdc25 and Wee1: analogous opposites?
    Cell Div. 2007 May 04;2:12 PMID: 17480229
  59. A chemical switch for inhibitor-sensitive alleles of any protein kinase.
    Nature. 2000 Sep 21;407(6802):395-401 PMID: 11014197
  60. cdc25 is a specific tyrosine phosphatase that directly activates p34cdc2.
    Cell. 1991 Oct 4;67(1):197-211 PMID: 1913817
  61. Nim1 kinase promotes mitosis by inactivating Wee1 tyrosine kinase.
    Nature. 1993 Jun 24;363(6431):738-41 PMID: 8515818
  62. Negative regulation of mitosis by wee1+, a gene encoding a protein kinase homolog.
    Cell. 1987 May 22;49(4):559-67 PMID: 3032459
  63. The morphogenesis checkpoint: how yeast cells watch their figures.
    Curr Opin Cell Biol. 2003 Dec;15(6):648-53 PMID: 14644188
  64. cdc25+ functions as an inducer in the mitotic control of fission yeast.
    Cell. 1986 Apr 11;45(1):145-53 PMID: 3955656
  65. Characterization of four B-type cyclin genes of the budding yeast Saccharomyces cerevisiae.
    Mol Biol Cell. 1992 Jul;3(7):805-18 PMID: 1387566
  66. Checking cell size in yeast.
    Trends Genet. 2002 Sep;18(9):479-85 PMID: 12175809
  67. Protein phosphatase 2A regulates MPF activity and sister chromatid cohesion in budding yeast.
    Curr Biol. 1996 Dec 1;6(12):1609-20 PMID: 8994825
  68. Morphogenesis in the yeast cell cycle: regulation by Cdc28 and cyclins.
    J Cell Biol. 1993 Mar;120(6):1305-20 PMID: 8449978
  69. CDC55, a Saccharomyces cerevisiae gene involved in cellular morphogenesis: identification, characterization, and homology to the B subunit of mammalian type 2A protein phosphatase.
    Mol Cell Biol. 1991 Nov;11(11):5767-80 PMID: 1656238
  70. 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
  71. A morphogenesis checkpoint monitors the actin cytoskeleton in yeast.
    J Cell Biol. 1998 Sep 21;142(6):1487-99 PMID: 9744879
  72. Saccharomyces cerevisiae homologs of mammalian B and B' subunits of protein phosphatase 2A direct the enzyme to distinct cellular functions.
    J Biol Chem. 1997 Mar 28;272(13):8256-62 PMID: 9079645
  73. Regulation of Mih1/Cdc25 by protein phosphatase 2A and casein kinase 1.
    J Cell Biol. 2008 Mar 10;180(5):931-45 PMID: 18316413
  74. Mutations in the Saccharomyces cerevisiae type 2A protein phosphatase catalytic subunit reveal roles in cell wall integrity, actin cytoskeleton organization and mitosis.
    Genetics. 1997 Feb;145(2):227-41 PMID: 9071579
  75. Loss of a protein phosphatase 2A regulatory subunit (Cdc55p) elicits improper regulation of Swe1p degradation.
    Mol Cell Biol. 2000 Nov;20(21):8143-56 PMID: 11027284
  76. CLB5 and CLB6, a new pair of B cyclins involved in DNA replication in Saccharomyces cerevisiae.
    Genes Dev. 1993 Jul;7(7A):1160-75 PMID: 8319908
  77. G2/M arrest caused by actin disruption is a manifestation of the cell size checkpoint in fission yeast.
    Mol Biol Cell. 2001 Dec;12(12):3892-903 PMID: 11739788
  78. Cdk1-dependent regulation of the mitotic inhibitor Wee1.
    Cell. 2005 Aug 12;122(3):407-20 PMID: 16096060
  79. Wee1-dependent mechanisms required for coordination of cell growth and cell division.
    J Cell Sci. 2003 Dec 15;116(Pt 24):4883-90 PMID: 14625382
  80. Control of mitotic events by Nap1 and the Gin4 kinase.
    J Cell Biol. 1997 Jul 14;138(1):119-30 PMID: 9214386
  81. Systematic identification of pathways that couple cell growth and division in yeast.
    Science. 2002 Jul 19;297(5580):395-400 PMID: 12089449
  82. Mitotic CDKs control the metaphase-anaphase transition and trigger spindle elongation.
    Genes Dev. 2008 Jun 1;22(11):1534-48 PMID: 18519644
Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1939-4586
DOI
10.1091/mbc.E10-06-0487
Published
2011-01-01
Epub
2010-00-30
Pages
20-32
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC3016974
Subset
IM
Grants
NIGMS NIH HHS · GM069062 · United States
External Links
PubMed source DOI: 10.1091/mbc.E10-06-0487 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