High impact information on CDC14

• During anaphase, Cdk- and Polo-dependent phosphorylation of Net1 is thought to release active Cdc14 [1].
• PP2A(Cdc55) downregulation also promotes phosphorylation of Bfa1, contributing to activation of the "mitotic exit network" that sustains Cdc14 as Cdk activity declines [1].
• In metaphase, Cdc14 is kept inactive in the nucleolus by its inhibitor Net1 [1].
• Separase, concomitantly with cleaving cohesin, activates the phosphatase Cdc14 [2].
• Cdc14 phosphatase induces rDNA condensation and resolves cohesin-independent cohesion during budding yeast anaphase [2].

Biological context of CDC14

• In contrast, the CDC14 protein acts after mitosis [3].
• We suggest that the CDC14 protein performs a function late in the cell cycle that may be required for efficient initiation of DNA replication during S phase of the next cell cycle [3].
• We found genetic interactions between CDC14 and the replication initiator gene CDC6, extending previous observations of interactions between the late mitotic function of Cdc14p and control of DNA replication [4].
• We confirmed that overexpression of CDC14 could rescue mutations in CDC15, which encodes another kinase also implicated to act in late M phase [5].
• The CaCDC14 gene shares 49% of amino acid sequence identity with the S. cerevisiae CDC14 gene, 46% with Schizosaccharomyces pombe homologue, 35% with Caenorhabditis elegans and 37% and 38% with human CDC14A and CDC14B genes, respectively [6].

Anatomical context of CDC14

• The Cdc14 liberation from the nucleolus was inhibited by the Mad2 checkpoint and by the Bub2 checkpoint in a different manner when microtubule organization was disrupted [7].
• In cdc14 and cdc15 mutants that arrest late in mitosis, the elongated nuclear envelope extension that stretches between daughter nuclei during telophase was preserved [8].
• Cdc14p localizes to the bud neck, among other cytoplasmic structures, following its release from the nucleolus in late anaphase [9].
• The Cdc14 dual-specificity phosphatases regulate key events in the eukaryotic cell cycle [10].

Associations of CDC14 with chemical compounds

• We report here that temperature-sensitive (ts) dhf2-2 mutant cells can be rescued by overexpression of CDC14, which encodes a dual-specificity protein phosphatase, when grown on glucose-containing medium, as reported previously, but not on galactose [11].
• CDC14 encodes a phosphotyrosine phosphatase (PTPase) and is essential for termination of M phase [12].
• Screening of two S. cerevisiae cDNA libraries led to the identification of CBT1 as a gene which, if overexpressed simultaneously with CDC14, results in the rescue of the dbJ2-2 mutation at restrictive temperature on galactose-based medium, as well as on media containing non-fermentable carbon sources such as glycerol, lactate and acetate [11].
• The essential CDC14 gene of the budding yeast, Saccharomyces cerevisiae, encodes a 62-kDa protein containing a sequence that conforms to the active site motif found in all enzymes of the protein tyrosine phosphatase superfamily [13].
• However, unlike histone mRNA, which is repressed upon hydroxyurea arrest, CDC14 mRNA appears to be unaffected [14].

Physical interactions of CDC14

• Regulation of the Bfa1p-Bub2p complex at spindle pole bodies by the cell cycle phosphatase Cdc14p [15].
• Here we show that Cdc14p contains a leucine-rich nuclear export signal (NES) that interacts with Crm1p physically [9].
• An analysis of truncation mutants indicates that the Cdc14 binding site is located within a segment of Net1 containing residues 1-341 [16].
• We report that, like Net1, Tof2 can bind to Cdc14 directly [17].

Enzymatic interactions of CDC14

• Cdc14 activates the degradation of Clb cyclins by dephosphorylating the APC-specificity factor Cdh1 [18].
• Cdc14p mediates mitotic exit by dephosphorylating Cdk1p substrates and promoting Cdk1p inactivation [19].
• Cdc14 dephosphorylated Sli15 and thereby directed the complex to spindles [20].

Regulatory relationships of CDC14

• An extra copy of CDC14 suppressed the temperature sensitivity of cdc15-rlt1 cells, but not that of cdc15-1 cells [12].
• The highly conserved protein phosphatase Cdc14 promotes both Clb degradation and Sic1 accumulation [18].
• The level of the CDC14 transcript appears to be weakly cell cycle-regulated and has a periodicity which lags approximately 15 min behind histone HTB1 mRNA accumulation levels [14].
• This delocalization of Cdc14 was suppressed by the deletion of SPO12 [21].
• From G1 through anaphase, RENT localizes to the nucleolus, and Cdc14 activity is inhibited by Net1 [22].

Other interactions of CDC14

• However, in cdc6 and cdc14 mutants, the mitotic loss of pDK243 with an ARS cluster was suppressed by a factor of 6-8 compared to pDK243 without the cluster [3].
• But how the MEN residing at the spindle pole body (SPB) controls the association of Cdc14 with Net1/Cfi1 in the nucleolus is not yet understood [7].
• We conclude that Cdc14 is released from the nucleolus at the onset of anaphase in a CDC5-dependent manner and that MEN factors possibly regulate Cdc14 release from the SPB [7].
• We provide evidence suggesting that Cdc14p is the phosphatase responsible for the dephosphorylation of Cdc15p [23].
• The SPB localization of Cdc14 was significantly affected by the MEN mutations and the bub2 mutation [7].

Analytical, diagnostic and therapeutic context of CDC14

• The sequence analysis of the C. albicans CDC14 gene reveals a putative open reading frame of 1626 base pairs interrupted by an intron located close to the 5' region [6].
• Using immunofluorescence microscopy and immunogold labeling, we demonstrate that a functional HA-tagged version of the phosphatase Cdc14 localizes to the nucleolus [24].
• The exit from mitosis is monitored by Cdc14 immunofluorescence and Clb2 Western blots [25].

References