| Structural highlights
4zj7 is a 2 chain structure with sequence from Baker's yeast. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Gene: | PSE1, KAP121, YMR308C, YM9952.10C (Baker's yeast), CDC14, OAF3, YFR028C (Baker's yeast) |
| Activity: | Protein-tyrosine-phosphatase, with EC number 3.1.3.48 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[IMB3_YEAST] Involved in the nuclear import of ribosomal proteins. Binds to nucleoporins and the GTP-bound form of GSP1 (Ran). Plays a role in protein secretion. [CDC14_YEAST] Protein phosphatase which antagonizes mitotic cyclin-dependent kinase CDC28, the inactivation of which is essential for exit from mitosis. To access its substrates, is released from nucleolar sequestration during mitosis. Plays an essential in coordinating the nuclear division cycle with cytokinesis through the cytokinesis checkpoint. Involved in chromosome segregation, where it is required for meiosis I spindle dissambly as well as for establishing two consecutive chromosome segregation phases. Allows damaged actomyosin rings to be maintained to facilitate completion of cell division in response to minor perturbation of the cell division machinery. Inhibits transcription of ribosomal genes (rDNA) during anaphase and controls segregation of nucleolus by facilitating condensin targeting to rDNA chromatin in anaphase. Dephosphorylates SIC1, a CDC28 inhibitor, and SWI5, a transcription factor for SIC1, and induces degradation of mitotic cyclins, likely by dephosphorylating the activator of mitotic cyclin degradation, CDH1. Dephosphorylates the microtubule bundling factor ASE1 which is required to define a centered and focused mitotic spindle midzone that can drive continuous spindle elongation. Dephosphorylates the anaphase-promoting complex inhibitor ACM1, leading to its degradation. Facilitates INN1-CYK3 complex formation which promotes cytokinesis through the dephosphosprylation of CDC28-phosphosphorylated INN1. Reverts also the inhibitory CDC28 phosphorylation of CHS2 for endoplasmic reticulum export, ensuring that septum formation is contingent upon chromosome separation and exit from mitosis. Additional substrates for CDC14 are the formins BNI1 and BNR1, as well as CDC6, DBP2, DSN1, INCENP, KAR9, MCM3, ORC2, ORC6, SLD2, and SWI6. Activity is inhibited by interaction with NET1 which sequesters it to the nucleolus.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] [23] [24] [25] [26] [27] [28] [29] [30]
Publication Abstract from PubMed
In Saccharomyces cerevisiae, the protein phosphatase Cdc14p is an antagonist of mitotic cyclin-dependent kinases and is a key regulator of late mitotic events such as chromosome segregation, spindle disassembly and cytokinesis. The activity of Cdc14p is controlled by cell-cycle dependent changes in its association with its competitive inhibitor Net1p (also known as Cfi1p) in the nucleolus. For most of the cell cycle up to metaphase, Cdc14p is sequestered in the nucleolus in an inactive state. During anaphase, Cdc14p is released from Net1p, spreads into the nucleus and cytoplasm, and dephosphorylates key mitotic targets. Although regulated nucleocytoplasmic shuttling of Cdc14p has been suggested to be important for exit from mitosis, the mechanism underlying Cdc14p nuclear trafficking remains poorly understood. Here we show that the C-terminal region (residues 517-551) of Cdc14p can function as a nuclear localization signal (NLS) in vivo and also binds to Kap121p (also known as Pse1p), an essential nuclear import carrier in yeast, in a Gsp1p-GTP-dependent manner in vitro. Moreover we report a crystal structure, at 2.4 A resolution, of Kap121p bound to the C-terminal region of Cdc14p. The structure and structure-based mutational analyses suggest that either the last five residues at the extreme C-terminus of Cdc14p (residues 547-551; Gly-Ser-Ile-Lys-Lys) or adjacent residues with similar sequence (residues 540-544; Gly-Gly-Ile-Arg-Lys) can bind to the NLS-binding site of Kap121p, with two residues (Ile in the middle and Lys at the end of the five residues) of Cdc14p making key contributions to the binding specificity. Based on comparison with other structures of Kap121p-ligand complexes, we propose "IK-NLS" as an appropriate term to refer to the Kap121p-specific NLS.
Crystal structure of the karyopherin Kap121p bound to the extreme C-terminus of the protein phosphatase Cdc14p.,Kobayashi J, Hirano H, Matsuura Y Biochem Biophys Res Commun. 2015 May 28. pii: S0006-291X(15)00983-3. doi:, 10.1016/j.bbrc.2015.05.060. PMID:26022122[31]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
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- ↑ Marston AL, Lee BH, Amon A. The Cdc14 phosphatase and the FEAR network control meiotic spindle disassembly and chromosome segregation. Dev Cell. 2003 May;4(5):711-26. PMID:12737806
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- ↑ Torres-Rosell J, Machin F, Jarmuz A, Aragon L. Nucleolar segregation lags behind the rest of the genome and requires Cdc14p activation by the FEAR network. Cell Cycle. 2004 Apr;3(4):496-502. Epub 2004 Apr 1. PMID:15004526
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- ↑ Wang BD, Yong-Gonzalez V, Strunnikov AV. Cdc14p/FEAR pathway controls segregation of nucleolus in S. cerevisiae by facilitating condensin targeting to rDNA chromatin in anaphase. Cell Cycle. 2004 Jul;3(7):960-7. Epub 2004 Jul 4. PMID:15190202
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- ↑ Tzeng YW, Huang JN, Schuyler SC, Wu CH, Juang YL. Functions of the mitotic B-type cyclins CLB1, CLB2, and CLB3 at mitotic exit antagonized by the CDC14 phosphatase. Fungal Genet Biol. 2011 Oct;48(10):966-78. doi: 10.1016/j.fgb.2011.07.001. Epub, 2011 Jul 19. PMID:21784165 doi:http://dx.doi.org/10.1016/j.fgb.2011.07.001
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- ↑ Bremmer SC, Hall H, Martinez JS, Eissler CL, Hinrichsen TH, Rossie S, Parker LL, Hall MC, Charbonneau H. Cdc14 phosphatases preferentially dephosphorylate a subset of cyclin-dependent kinase (Cdk) sites containing phosphoserine. J Biol Chem. 2012 Jan 13;287(3):1662-9. doi: 10.1074/jbc.M111.281105. Epub 2011, Nov 23. PMID:22117071 doi:http://dx.doi.org/10.1074/jbc.M111.281105
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- ↑ Sanchez-Diaz A, Nkosi PJ, Murray S, Labib K. The Mitotic Exit Network and Cdc14 phosphatase initiate cytokinesis by counteracting CDK phosphorylations and blocking polarised growth. EMBO J. 2012 Aug 29;31(17):3620-34. doi: 10.1038/emboj.2012.224. Epub 2012 Aug 7. PMID:22872148 doi:http://dx.doi.org/10.1038/emboj.2012.224
- ↑ Schild D, Byers B. Diploid spore formation and other meiotic effects of two cell-division-cycle mutations of Saccharomyces cerevisiae. Genetics. 1980 Dec;96(4):859-76. PMID:7021319
- ↑ Shirayama M, Matsui Y, Toh-e A. Dominant mutant alleles of yeast protein kinase gene CDC15 suppress the lte1 defect in termination of M phase and genetically interact with CDC14. Mol Gen Genet. 1996 May 23;251(2):176-85. PMID:8668128
- ↑ Taylor GS, Liu Y, Baskerville C, Charbonneau H. The activity of Cdc14p, an oligomeric dual specificity protein phosphatase from Saccharomyces cerevisiae, is required for cell cycle progression. J Biol Chem. 1997 Sep 19;272(38):24054-63. PMID:9295359
- ↑ Visintin R, Craig K, Hwang ES, Prinz S, Tyers M, Amon A. The phosphatase Cdc14 triggers mitotic exit by reversal of Cdk-dependent phosphorylation. Mol Cell. 1998 Dec;2(6):709-18. PMID:9885559
- ↑ Kobayashi J, Hirano H, Matsuura Y. Crystal structure of the karyopherin Kap121p bound to the extreme C-terminus of the protein phosphatase Cdc14p. Biochem Biophys Res Commun. 2015 May 28. pii: S0006-291X(15)00983-3. doi:, 10.1016/j.bbrc.2015.05.060. PMID:26022122 doi:http://dx.doi.org/10.1016/j.bbrc.2015.05.060
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