Home LiteratureArticle Details
PMID: 11448992 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Activity of the APC(Cdh1) form of the anaphase-promoting complex persists until S phase and prevents the premature expression of Cdc20p.

The Journal of cell biology ·Vol. 154 ·No. 1 ·2001-07-09 ·Pages 85-94

Huang JN, Park I, Ellingson E, Littlepage LE, Pellman D

Abstract

Cell cycle progression is driven by waves of cyclin expression coupled with regulated protein degradation. An essential step for initiating mitosis is the inactivation of proteolysis mediated by the anaphase-promoting complex/cyclosome (APC/C) bound to its regulator Cdh1p/Hct1p. Yeast APC(Cdh1) was proposed previously to be inactivated at Start by G1 cyclin/cyclin-dependent kinase (CDK). Here, we demonstrate that in a normal cell cycle APC(Cdh1) is inactivated in a graded manner and is not extinguished until S phase. Complete inactivation of APC(Cdh1) requires S phase cyclins. Further, persistent APC(Cdh1) activity throughout G1 helps to ensure the proper timing of Cdc20p expression. This suggests that S phase cyclins have an important role in allowing the accumulation of mitotic cyclins and further suggests a regulatory loop among S phase cyclins, APC(Cdh1), and APC(Cdc20).

MeSH Terms
Anaphase-Promoting Complex-Cyclosome Blotting, Northern Cdc20 Proteins Cdh1 Proteins Cell Cycle Cell Cycle Proteins/metabolism Cloning, Molecular Cyclin B/metabolism Cyclin-Dependent Kinase Inhibitor Proteins Flow Cytometry Fungal Proteins/metabolism,physiology Ligases/metabolism Microscopy, Fluorescence Mitosis Mutagenesis, Site-Directed Mutation Precipitin Tests Protein Structure, Tertiary Saccharomyces cerevisiae Proteins Saccharomycetales Time Factors Ubiquitin-Protein Ligase Complexes Ubiquitin-Protein Ligases
Chemicals
CDC20 protein, S cerevisiae CDH1 protein, S cerevisiae CLB2 protein, S cerevisiae Cdc20 Proteins Cdh1 Proteins Cell Cycle Proteins Cyclin B Cyclin-Dependent Kinase Inhibitor Proteins Fungal Proteins SIC1 protein, S cerevisiae Saccharomyces cerevisiae Proteins Ubiquitin-Protein Ligase Complexes Anaphase-Promoting Complex-Cyclosome Ubiquitin-Protein Ligases Ligases
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Huang J N
Department of Pediatric Oncology, The Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA.
Park I
Ellingson E
Littlepage L E
Pellman D
References (46)
46 references, click to expand
  1. Accumulation of cyclin B1 requires E2F and cyclin-A-dependent rearrangement of the anaphase-promoting complex.
    Nature. 1999 Oct 21;401(6755):815-8 PMID: 10548110
  2. The spindle checkpoint.
    Curr Opin Genet Dev. 1999 Feb;9(1):69-75 PMID: 10072359
  3. Inhibitory phosphorylation of the APC regulator Hct1 is controlled by the kinase Cdc28 and the phosphatase Cdc14.
    Curr Biol. 1999 Mar 11;9(5):227-36 PMID: 10074450
  4. Exit from mitosis is triggered by Tem1-dependent release of the protein phosphatase Cdc14 from nucleolar RENT complex.
    Cell. 1999 Apr 16;97(2):233-44 PMID: 10219244
  5. Subunits and substrates of the anaphase-promoting complex.
    Exp Cell Res. 1999 May 1;248(2):339-49 PMID: 10222126
  6. Cell cycle regulation of DNA replication initiator factor Dbf4p.
    Mol Cell Biol. 1999 Jun;19(6):4270-8 PMID: 10330168
  7. Cell cycle control of Cdc7p kinase activity through regulation of Dbf4p stability.
    Mol Cell Biol. 1999 Jul;19(7):4888-96 PMID: 10373538
  8. Phosphorylation of the cyclosome is required for its stimulation by Fizzy/cdc20.
    Biochem Biophys Res Commun. 1999 Jun 24;260(1):193-8 PMID: 10381365
  9. Regulation of APC activity by phosphorylation and regulatory factors.
    J Cell Biol. 1999 Aug 23;146(4):791-800 PMID: 10459014
  10. Whose end is destruction: cell division and the anaphase-promoting complex.
    Genes Dev. 1999 Aug 15;13(16):2039-58 PMID: 10465783
  11. 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
  12. The KEN box: an APC recognition signal distinct from the D box targeted by Cdh1.
    Genes Dev. 2000 Mar 15;14(6):655-65 PMID: 10733526
  13. Mitotic regulation of the APC activator proteins CDC20 and CDH1.
    Mol Biol Cell. 2000 May;11(5):1555-69 PMID: 10793135
  14. Hsl1p, a Swe1p inhibitor, is degraded via the anaphase-promoting complex.
    Mol Cell Biol. 2000 Jul;20(13):4614-25 PMID: 10848588
  15. 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
  16. Nonperiodic activity of the human anaphase-promoting complex-Cdh1 ubiquitin ligase results in continuous DNA synthesis uncoupled from mitosis.
    Mol Cell Biol. 2000 Oct;20(20):7613-23 PMID: 11003657
  17. Cell-cycle regulation of yeast histone mRNA.
    Cell. 1981 May;24(2):367-75 PMID: 7016339
  18. Two nuclear mutations that block mitochondrial protein import in yeast.
    Proc Natl Acad Sci U S A. 1984 Aug;81(15):4819-23 PMID: 6235522
  19. Isolation of monoclonal antibodies specific for human c-myc proto-oncogene product.
    Mol Cell Biol. 1985 Dec;5(12):3610-6 PMID: 3915782
  20. Purification of a RAS-responsive adenylyl cyclase complex from Saccharomyces cerevisiae by use of an epitope addition method.
    Mol Cell Biol. 1988 May;8(5):2159-65 PMID: 2455217
  21. Immunofluorescence methods for yeast.
    Methods Enzymol. 1991;194:565-602 PMID: 2005809
  22. CLB5: a novel B cyclin from budding yeast with a role in S phase.
    Genes Dev. 1992 Sep;6(9):1695-706 PMID: 1387626
  23. 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
  24. Closing the cell cycle circle in yeast: G2 cyclin proteolysis initiated at mitosis persists until the activation of G1 cyclins in the next cycle.
    Cell. 1994 Jul 1;77(7):1037-50 PMID: 8020094
  25. The B-type cyclin kinase inhibitor p40SIC1 controls the G1 to S transition in S. cerevisiae.
    Cell. 1994 Oct 21;79(2):233-44 PMID: 7954792
  26. Regulatable promoters of Saccharomyces cerevisiae: comparison of transcriptional activity and their use for heterologous expression.
    Nucleic Acids Res. 1994 Dec 25;22(25):5767-8 PMID: 7838736
  27. CDC27Hs colocalizes with CDC16Hs to the centrosome and mitotic spindle and is essential for the metaphase to anaphase transition.
    Cell. 1995 Apr 21;81(2):261-8 PMID: 7736578
  28. Genes involved in sister chromatid separation are needed for B-type cyclin proteolysis in budding yeast.
    Cell. 1995 Apr 21;81(2):269-78 PMID: 7736579
  29. A 20S complex containing CDC27 and CDC16 catalyzes the mitosis-specific conjugation of ubiquitin to cyclin B.
    Cell. 1995 Apr 21;81(2):279-88 PMID: 7736580
  30. The cyclosome, a large complex containing cyclin-selective ubiquitin ligase activity, targets cyclins for destruction at the end of mitosis.
    Mol Biol Cell. 1995 Feb;6(2):185-97 PMID: 7787245
  31. Two microtubule-associated proteins required for anaphase spindle movement in Saccharomyces cerevisiae.
    J Cell Biol. 1995 Sep;130(6):1373-85 PMID: 7559759
  32. Anaphase initiation in Saccharomyces cerevisiae is controlled by the APC-dependent degradation of the anaphase inhibitor Pds1p.
    Genes Dev. 1996 Dec 15;10(24):3081-93 PMID: 8985178
  33. APC-mediated proteolysis of Ase1 and the morphogenesis of the mitotic spindle.
    Science. 1997 Feb 28;275(5304):1311-4 PMID: 9036857
  34. Regulation of B-type cyclin proteolysis by Cdc28-associated kinases in budding yeast.
    EMBO J. 1997 May 15;16(10):2693-702 PMID: 9184216
  35. The anaphase-promoting complex is required in G1 arrested yeast cells to inhibit B-type cyclin accumulation and to prevent uncontrolled entry into S-phase.
    J Cell Sci. 1997 Jul;110 ( Pt 13):1523-31 PMID: 9224769
  36. Yeast Hct1 is a regulator of Clb2 cyclin proteolysis.
    Cell. 1997 Aug 22;90(4):683-93 PMID: 9288748
  37. Phosphorylation of Sic1p by G1 Cdk required for its degradation and entry into S phase.
    Science. 1997 Oct 17;278(5337):455-60 PMID: 9334303
  38. CDC20 and CDH1: a family of substrate-specific activators of APC-dependent proteolysis.
    Science. 1997 Oct 17;278(5337):460-3 PMID: 9334304
  39. The Polo-like kinase Cdc5p and the WD-repeat protein Cdc20p/fizzy are regulators and substrates of the anaphase promoting complex in Saccharomyces cerevisiae.
    EMBO J. 1998 Mar 2;17(5):1336-49 PMID: 9482731
  40. Proteolysis and the G1-S transition: the SCF connection.
    Curr Opin Genet Dev. 1998 Feb;8(1):36-42 PMID: 9529603
  41. The Polo-related kinase Cdc5 activates and is destroyed by the mitotic cyclin destruction machinery in S. cerevisiae.
    Curr Biol. 1998 Apr 23;8(9):497-507 PMID: 9560342
  42. The regulation of Cdc20 proteolysis reveals a role for APC components Cdc23 and Cdc27 during S phase and early mitosis.
    Curr Biol. 1998 Jun 18;8(13):750-60 PMID: 9651679
  43. Control of cyclin ubiquitination by CDK-regulated binding of Hct1 to the anaphase promoting complex.
    Science. 1998 Nov 27;282(5394):1721-4 PMID: 9831566
  44. The phosphatase Cdc14 triggers mitotic exit by reversal of Cdk-dependent phosphorylation.
    Mol Cell. 1998 Dec;2(6):709-18 PMID: 9885559
  45. SCF and APC: the Yin and Yang of cell cycle regulated proteolysis.
    Curr Opin Cell Biol. 1998 Dec;10(6):759-68 PMID: 9914180
  46. Dbf4p, an essential S phase-promoting factor, is targeted for degradation by the anaphase-promoting complex.
    Mol Cell Biol. 2000 Jan;20(1):242-8 PMID: 10594027
Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
Published
2001-07-09
Pages
85-94
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2196868
Subset
IM
Grants
NICHD NIH HHS · K08 HD01203 · United States
NICHD NIH HHS · P30 HD27823-10 · United States
NIGMS NIH HHS · R01 GM55772 · United States
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