CDC14/YFR028C Summary Help

Standard Name CDC14 1
Systematic Name YFR028C
Alias OAF3
Feature Type ORF, Verified
Description Protein phosphatase required for mitotic exit; located in the nucleolus until liberated by the FEAR and Mitotic Exit Network in anaphase, enabling it to act on key substrates to effect a decrease in CDK/B-cyclin activity and mitotic exit; required for meiosis I spindle disassembly; released from nucleolus upon entry into anaphase I of meiosis, resequestered in metaphase II, then released again upon entry into anaphase II; maintained in nucleolus by Cdc55p in early meiosis (2, 3, 4, 5, 6, 7 and see Summary Paragraph)
Name Description Cell Division Cycle 8
Chromosomal Location
ChrVI:210068 to 208413 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Gbrowse
Genetic position: 36 cM
Gene Ontology Annotations All CDC14 GO evidence and references
  View Computational GO annotations for CDC14
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
High-throughput
Regulatory Role
Regulatory modules predicted: stressResponse (601, 403)
Mutant phenotypes All CDC14 Phenotype evidence and references
Classical genetics
conditional
null
repressible
Large-scale survey
conditional
null
overexpression
reduction of function
repressible
Resources
interactions All CDC14 Interaction evidence and references
431 total interaction(s) for 236 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 152
  • Affinity Capture-RNA: 1
  • Affinity Capture-Western: 45
  • Biochemical Activity: 27
  • Co-localization: 6
  • PCA: 3
  • Reconstituted Complex: 17
  • Two-hybrid: 23
Genetic Interactions
  • Dosage Lethality: 8
  • Dosage Rescue: 37
  • Negative Genetic: 17
  • Phenotypic Enhancement: 17
  • Phenotypic Suppression: 19
  • Positive Genetic: 3
  • Synthetic Growth Defect: 18
  • Synthetic Lethality: 21
  • Synthetic Rescue: 17
Resources
Expression Summary
histogram
Resources
Protein Information All CDC14 Protein evidence and references
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrVI:210068 to 208413 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
SGD ORF map
Genetic position: 36 cM
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Relative
Coordinates		 Chromosomal
Coordinates		 Most Recent Updates
Coordinates Sequence
CDS 1..1656 210068..208413 2011-02-03 1996-07-31
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
Resources
External Links All Associated Seq | E.C. | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000001924
SUMMARY PARAGRAPH for CDC14

CDC14 encodes a protein phosphatase that is essential for mitotic exit and meiotic progression (9, 4, 10). Cdc14p dephosphorylates key mitotic targets which leads to the coordinated inactivation of mitotic cyclins, proper spindle disassembly, and completion of cytokinesis (3, 11, 12). During the meiotic cell cycle, Cdc14p has been proposed to coordinate spindle disassembly and the two consecutive chromosome segregation events (6, 13).

During most of the mitotic cell cycle, Cdc14p is kept inactive and sequestered in the nucleolus by Net1p as part of the RENT complex (14, 15, 16). Two regulatory networks, FEAR (CDC Fourteen Early Anaphase Release) and MEN (Mitotic Exit Network), coordinate the stepwise nucleolar release and activation of Cdc14p (17, 18, 19, 20, 21). Nucleolar release of Cdc14p requires its dissociation from Net1p and inactivation of its nuclear-localization signal via Dbf2p-mediated phosphorylation (22, 23, 24, 25, 26, 27). Cdc14p first relocates to the spindle pole body during early anaphase and then to the bud neck and cytoplasm during late anaphase (27, 18). Released from the nucleolus, Cdc14p can dephosphorylate S-phase and M-phase mitotic cyclin substrates to coordinate the metaphase to anaphase transition (28, 29, 20). The return of Cdc14p to the nucleolus signals the completion of mitosis (30, 31). Multiple regulatory pathways have been proposed to regulate Cdc14p phosphatase activity during meiosis as well (32, 33).

Cdc14p belongs to a subfamily of dual-specificity protein phosphatases that can dephosphorylate phosphotyrosine and phosphoserine/phosphothreonine residues (34). Cdc14p is conserved in fungi, worms, and mammals (35, 36, 37).

Last updated: 2010-05-18

References cited on this page View Complete Literature Guide for CDC14
1) Culotti J and Hartwell LH  (1971) Genetic control of the cell division cycle in yeast. 3. Seven genes controlling nuclear division. Exp Cell Res 67(2):389-401
2) Wan J, et al.  (1992) CDC14 of Saccharomyces cerevisiae. Cloning, sequence analysis, and transcription during the cell cycle. J Biol Chem 267(16):11274-80
3) Visintin R, et al.  (1998) The phosphatase Cdc14 triggers mitotic exit by reversal of Cdk-dependent phosphorylation. Mol Cell 2(6):709-18
4) Taylor GS, et al.  (1997) The activity of Cdc14p, an oligomeric dual specificity protein phosphatase from Saccharomyces cerevisiae, is required for cell cycle progression. J Biol Chem 272(38):24054-63
5) Saunders WS  (2002) The FEAR factor. Mol Cell 9(2):207-9
6) Marston AL, et al.  (2003) The Cdc14 phosphatase and the FEAR network control meiotic spindle disassembly and chromosome segregation. Dev Cell 4(5):711-26
7) Bizzari F and Marston AL  (2011) Cdc55 coordinates spindle assembly and chromosome disjunction during meiosis. J Cell Biol 193(7):1213-28
8) Hartwell LH, et al.  (1970) Genetic control of the cell-division cycle in yeast. I. Detection of mutants. Proc Natl Acad Sci U S A 66(2):352-9
9) Schild D and Byers B  (1980) Diploid spore formation and other meiotic effects of two cell-division-cycle mutations of Saccharomyces cerevisiae. Genetics 96(4):859-76
10) Stegmeier F and Amon A  (2004) Closing mitosis: the functions of the Cdc14 phosphatase and its regulation. Annu Rev Genet 38():203-32
11) Khmelinskii A and Schiebel E  (2008) Assembling the spindle midzone in the right place at the right time. Cell Cycle 7(3):283-6
12) Hall MC, et al.  (2008) Cdc28 and Cdc14 control stability of the anaphase-promoting complex inhibitor Acm1. J Biol Chem 283(16):10396-407
13) Buonomo SB, et al.  (2003) Division of the nucleolus and its release of CDC14 during anaphase of meiosis I depends on separase, SPO12, and SLK19. Dev Cell 4(5):727-39
14) Shou W, et al.  (1999) Exit from mitosis is triggered by Tem1-dependent release of the protein phosphatase Cdc14 from nucleolar RENT complex. Cell 97(2):233-44
15) Visintin R, et al.  (1999) Cfi1 prevents premature exit from mitosis by anchoring Cdc14 phosphatase in the nucleolus. Nature 398(6730):818-23
16) Traverso EE, et al.  (2001) Characterization of the Net1 cell cycle-dependent regulator of the Cdc14 phosphatase from budding yeast. J Biol Chem 276(24):21924-31
17) Stegmeier F, et al.  (2002) Separase, polo kinase, the kinetochore protein Slk19, and Spo12 function in a network that controls Cdc14 localization during early anaphase. Cell 108(2):207-20
18) Yoshida S, et al.  (2002) Mitotic exit network controls the localization of Cdc14 to the spindle pole body in Saccharomyces cerevisiae. Curr Biol 12(11):944-50
19) Visintin R, et al.  (2003) The role of the polo kinase Cdc5 in controlling Cdc14 localization. Mol Biol Cell 14(11):4486-98
20) Jin F, et al.  (2008) Temporal control of the dephosphorylation of Cdk substrates by mitotic exit pathways in budding yeast. Proc Natl Acad Sci U S A 105(42):16177-82
21) Jin F, et al.  (2009) The multilayer regulation of the metaphase-to-anaphase transition. Cell Cycle 8(5):700-4
22) Yoshida S and Toh-e A  (2002) Budding yeast Cdc5 phosphorylates Net1 and assists Cdc14 release from the nucleolus. Biochem Biophys Res Commun 294(3):687-91
23) Bembenek J, et al.  (2005) Crm1-mediated nuclear export of Cdc14 is required for the completion of cytokinesis in budding yeast. Cell Cycle 4(7):961-71
24) Stoepel J, et al.  (2005) The mitotic exit network Mob1p-Dbf2p kinase complex localizes to the nucleus and regulates passenger protein localization. Mol Biol Cell 16(12):5465-79
25) Yellman CM and Burke DJ  (2006) The role of Cdc55 in the spindle checkpoint is through regulation of mitotic exit in Saccharomyces cerevisiae. Mol Biol Cell 17(2):658-66
26) Queralt E, et al.  (2006) Downregulation of PP2A(Cdc55) phosphatase by separase initiates mitotic exit in budding yeast. Cell 125(4):719-32
27) Mohl DA, et al.  (2009) Dbf2-Mob1 drives relocalization of protein phosphatase Cdc14 to the cytoplasm during exit from mitosis. J Cell Biol 184(4):527-39
28) Bloom J and Cross FR  (2007) Novel role for Cdc14 sequestration: Cdc14 dephosphorylates factors that promote DNA replication. Mol Cell Biol 27(3):842-53
29) Queralt E and Uhlmann F  (2008) Cdk-counteracting phosphatases unlock mitotic exit. Curr Opin Cell Biol 20(6):661-8
30) Wang Y, et al.  (2003) Exit from exit: resetting the cell cycle through Amn1 inhibition of G protein signaling. Cell 112(5):697-709
31) Visintin C, et al.  (2008) APC/C-Cdh1-mediated degradation of the Polo kinase Cdc5 promotes the return of Cdc14 into the nucleolus. Genes Dev 22(1):79-90
32) McDonald CM, et al.  (2005) The Ama1-directed anaphase-promoting complex regulates the Smk1 mitogen-activated protein kinase during meiosis in yeast. Genetics 171(3):901-11
33) Holt LJ, et al.  (2007) Evolution of Ime2 phosphorylation sites on Cdk1 substrates provides a mechanism to limit the effects of the phosphatase Cdc14 in meiosis. Mol Cell 25(5):689-702
34) Patterson KI, et al.  (2009) Dual-specificity phosphatases: critical regulators with diverse cellular targets. Biochem J 418(3):475-89
35) Trautmann S and McCollum D  (2005) Distinct nuclear and cytoplasmic functions of the S. pombe Cdc14-like phosphatase Clp1p/Flp1p and a role for nuclear shuttling in its regulation. Curr Biol 15(15):1384-9
36) Gruneberg U, et al.  (2002) The CeCDC-14 phosphatase is required for cytokinesis in the Caenorhabditis elegans embryo. J Cell Biol 158(5):901-14
37) Esteban V, et al.  (2006) Human Cdc14A reverses CDK1 phosphorylation of Cdc25A on serines 115 and 320. Cell Cycle 5(24):2894-8