High impact information on CDC15

• We find that daughter cells activate an Antagonist of MEN pathway (AMEN) in part through induction of the Amn1 protein that binds directly to Tem1 and prevents its association with its target kinase Cdc15 [1].
• Apical polarization was delayed in cdc15 mutants as compared with budding in control cells and this delay was abolished in a septin mutant [2].
• We report here that lyt1 is an allele of cdc15, a gene which encodes a protein kinase that functions late in the cell cycle [2].
• To learn more about the biochemical composition and activity of this ring, we have characterized the in vivo distribution and function of Cyk2p, a budding yeast protein that exhibits significant sequence similarity to the cdc15/PSTPIP family of cleavage furrow proteins [3].
• However, in cells arrested in late mitosis (M) by a cdc15 mutation, the unique DNA appeared decondensed while the repetitive rDNA region appeared condensed, suggesting that the condensation state of separate regions of the genome may be regulated differently [4].

Biological context of CDC15

• We propose that mitosis progression and the M/G1 phase transition specifically depend on cell growth through a mechanism modulated by PKAs and interacting with the APC/CDC15/CDC5 mitotic system [5].
• We confirmed that overexpression of CDC14 could rescue mutations in CDC15, which encodes another kinase also implicated to act in late M phase [6].
• Here, we report that both the phosphorylation and localization of Cdc15p are cell cycle regulated [7].
• The extent of phosphorylation of Cdc15p gradually increases during cell-cycle progression until some point during late anaphase/telophase when it is rapidly dephosphorylated [7].
• We find that Cdc15 is recruited to both spindle pole bodies (SPBs) during anaphase [8].

Anatomical context of CDC15

• Cdc15 was present at the SPB of the mother cell until late mitosis, when it also associated with the daughter pole [9].
• FBP17 consists of a C-terminal Src homology 3 domain and an N-terminal region that is homologous to the cell division cycle protein, cdc15, a regulator of the actin cytoskeleton in Schizosaccharomyces pombe [10].
• We have constructed a Xenopus oocyte cDNA library in a Saccharomyces cerevisiae expression vector and used this library to isolate genes that can function in yeast cells to suppress the temperature sensitive [corrected] defect of the cdc15 mutation [11].
• In cdc14 and cdc15 mutants that arrest late in mitosis, the elongated nuclear envelope extension that stretches between daughter nuclei during telophase was preserved [12].

Associations of CDC15 with chemical compounds

• The amino acid sequence of the 974 amino acids/110 kDa CDC15 gene product, as deduced from the nucleotide sequence, includes an aminoterminal protein kinase domain which contains a primary sequence mosaic showing patterns specific for protein serine/threonine kinases besides those for protein tyrosine kinases [13].
• Furthermore, we show that lowering cAMP levels is sufficient to allow cells with a nonfunctional Cdc15 protein to complete the mitotic cycle [11].
• Moreover, Mob1p, but not Cdc15p, is required for dissociating Aurora from the kinetochore region [14].
• We identified an Arabidopsis thaliana gene, AtMAP3Kepsilon1, and a Brassica napus cDNA, BnMAP3Kepsilon1, encoding functional protein serine/threonine kinases closely related to cdc7p and Cdc15p from Schizosaccharomyces pombe and Saccharomyces cerevisiae, respectively [15].

Physical interactions of CDC15

• Thus, in nud1-2 cells the failure of Tem1p to interact with Cdc15p at the SPB probably prevents mitotic exit [16].
• As a consequence, Cdc15 binds to the daughter pole and triggers cytokinesis [9].

Regulatory relationships of CDC15

• An extra copy of CDC14 suppressed the temperature sensitivity of cdc15-rlt1 cells, but not that of cdc15-1 cells [17].
• Dominant mutant alleles of yeast protein kinase gene CDC15 suppress the lte1 defect in termination of M phase and genetically interact with CDC14 [17].
• Thus, Cdc15 promotes the exit from mitosis by directly switching on the kinase activity of Dbf2 [18].
• The defect of TEM1 was suppressed by a high dose of CDC15, which encodes a protein kinase homologous to mitogen-activated protein kinase kinase kinases [19].

Other interactions of CDC15

• Both events depend on the mitotic exit pathway components TEM1 and CDC15 [8].
• Regulation of the mitotic exit protein kinases Cdc15 and Dbf2 [8].
• The cdc15 mutations thus isolated were recessive with regard to the temperature-sensitive phenotype and were dominant with respect to suppression of lte1 [17].
• At the end of telophase, a portion of Cdc15p is located at the mother-bud neck, suggesting a possible role for Cdc15p in cytokinesis [7].
• Using a Cdc15p fusion protein coupled at its carboxyl terminus to green fluorescent protein (GFP), we found that Cdc15p, like its homologue Cdc7p [8] in fission yeast, localizes to the spindle pole bodies (SPBs) during mitosis [7].

Analytical, diagnostic and therapeutic context of CDC15

• Molecular cloning of chromosome I DNA from Saccharomyces cerevisiae: isolation and analysis of the CEN1-ADE1-CDC15 region [20].
• Finally, RNA blot hybridization and electron microscopy of R-loop-containing DNA were used to map transcribed regions in the 23 kilobases of DNA that went from CEN1 to CDC15 [20].
• To this end, we used DNA microarrays and samples from yeast cultures synchronized by three independent methods: alpha factor arrest, elutriation, and arrest of a cdc15 temperature-sensitive mutant [21].
• CDC6 mRNA accumulates in cdc15-arrested telophase cells, decays around cell separation, and reappears during telophase and nuclear division of the next cycle [22].

References