| Structural highlights
Function
[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] [SWI6_YEAST] Part of a complex involved in cell-cycle-dependent transcription. SWI4 and SWI6 are required for formation of the cell-cycle box factor-DNA complex. The repeated element in the upstream region of HO (5'-CACGAAAA-3') is called the cell cycle box (CCB).
Publication Abstract from PubMed
In the budding yeast Saccharomyces cerevisiae, the protein phosphatase Cdc14p orchestrates various events essential for mitotic exit. We have determined the X-ray crystal structures at 1.85 A resolution of the catalytic domain of Cdc14p in both the apo state, and as a complex with S160-phosphorylated Swi6p peptide. Each asymmetric unit contains two Cdc14p chains arranged in an intimately associated homodimer, consistent with its oligomeric state in solution. The dimerization interface is located on the backside of the substrate-binding cleft. Structure-based mutational analyses indicate that the dimerization of Cdc14p is required for normal growth of yeast cells.
Structure and dimerization of the catalytic domain of the protein phosphatase Cdc14p, a key regulator of mitotic exit in Saccharomyces cerevisiae.,Kobayashi J, Matsuura Y Protein Sci. 2017 Oct;26(10):2105-2112. doi: 10.1002/pro.3244. Epub 2017 Aug 22. PMID:28758351[31]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
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- ↑ 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, Matsuura Y. Structure and dimerization of the catalytic domain of the protein phosphatase Cdc14p, a key regulator of mitotic exit in Saccharomyces cerevisiae. Protein Sci. 2017 Oct;26(10):2105-2112. doi: 10.1002/pro.3244. Epub 2017 Aug 22. PMID:28758351 doi:http://dx.doi.org/10.1002/pro.3244
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