High impact information on CDC5

• Condensin enhances the association of Cdc5 with chromosomes and its phosphorylation of cohesin, which in turn likely stimulates cohesin removal [1].
• Here we use budding yeast Saccharomyces cerevisiae to show that condensin and Cdc5, a Polo-like kinase, facilitate the removal of cohesin from chromosomes prior to the onset of anaphase I when homologs segregate [1].
• Condensin/Cdc5-dependent removal of cohesin underscores the potential importance of crosstalk between chromosome structural components in chromosome morphogenesis and provides a mechanism to couple chromosome morphogenesis with other meiotic events [1].
• Cdc5 phosphorylates Bfa1 and acts to antagonize Bfa1 function to promote mitotic exit [2].
• Regulation of the Bub2/Bfa1 GAP complex by Cdc5 and cell cycle checkpoints [2].

Biological context of CDC5

• CDC5 and CKII control adaptation to the yeast DNA damage checkpoint [3].
• Consistent with the function at the G2/M boundary, the CDC5 transcript accumulated periodically during the cell cycle, peaking at the G2/M boundary [4].
• An activity that phosphorylated exogenously added casein was immunoprecipitated by antiserum against a TrpE-Cdc5 fusion protein from lysates of wild-type cells containing CDC5 on a multicopy plasmid but not of cells bearing a small deletion in the predicted protein kinase domain of CDC5 on the plasmid [4].
• 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 [5].
• Overexpression of CDC5 resulted in increased APC activity and mitotic cyclin destruction in asynchronous cells or in cells arrested in metaphase [6].

Anatomical context of CDC5

• Mammalian CDC5 colocalizes with pre-mRNA splicing factors in the nuclei of mammalian cells, associates with core components of the splicing machinery in nuclear extracts, and interacts with the spliceosome throughout the splicing reaction in vitro [7].
• These data provide evidence that eukaryotic cells require CDC5 proteins for pre-mRNA splicing [7].

Associations of CDC5 with chemical compounds

• Accordingly, replacing with alanines five serine residues belonging to Polo kinase-dependent putative phosphorylation sites dramatically reduces Mad3 phosphorylation, suggesting that Mad3 is likely an in vivo target of Cdc5 [8].
• PLK (polo-like kinase) belongs to a family of serine/threonine kinases and represents the human counterpart of polo in Drosophila melanogaster and of CDC5 in Saccharomyces cerevisiae [9].
• We found that budding yeast Polo-like kinase Cdc5 controls the targeting and activation of Rho1 (RhoA) at the division site via Rho1 guanine nucleotide exchange factors [10].

Physical interactions of CDC5

• At least 26 proteins were detected in the Cdc5p/Cef1p complexes [11].
• We had previously shown that Dbf4p interacts with the M phase polo-like kinase Cdc5p, a key regulator of the APC late in mitosis [12].

Enzymatic interactions of CDC5

• CONCLUSIONS: We propose that although Cdc5 potentially disassembles RENT by directly phosphorylating Net1, Cdc5 mediates exit from mitosis primarily by phosphorylating other targets [13].

Regulatory relationships of CDC5

• Bfa1 has been identified as a regulatory target of Cdc5 but there are conflicting deductions from indirect in vivo assays as to whether phosphorylation inhibits or stimulates Bfa1 activity [14].
• Evidence suggests that Rad53 exerts its role in checkpoint control through regulation of the Polo kinase Cdc5 [15].
• Cdc5 influences phosphorylation of Net1 and disassembly of the RENT complex [13].
• In particular, we find that Cdc5p is temporally recruited to promoters of the cell-cycle-regulated CLB2 gene cluster, where it targets the Mcm1p-Fkh2p-Ndd1p transcription factor complex, through direct phosphorylation of the coactivator protein Ndd1p [16].
• In addition to localizing at the spindle poles and cytokinetic neck filaments, Cdc5 induces and localizes to additional septin ring structures within the elongated buds [17].

Other interactions of CDC5

• We show that one mutation resides in CDC5, which encodes a polo-like kinase, whereas a second, less penetrant, adaptation-defective mutant is affected at the CKB2 locus, which encodes a nonessential specificity subunit of casein kinase II [3].
• We show that, like cdc28 mutants, cdc5 mutants affect APC phosphorylation in vivo [18].
• A multicopy suppressor gene of the Saccharomyces cerevisiae G1 cell cycle mutant gene dbf4 encodes a protein kinase and is identified as CDC5 [4].
• Thus, in vivo inactivation of Bfa1-Bub2 by Cdc5 would have a positive regulatory effect by increasing levels of Tem1-GTP so stimulating exit from mitosis [14].
• Cyclin-specific APC activity in cells overexpressing CDC5 was reduced in the absence of the APC regulatory proteins Hct 1 and Cdc20 [6].

Analytical, diagnostic and therapeutic context of CDC5

• Novel functional dissection of the localization-specific roles of budding yeast polo kinase Cdc5p [19].
• Using transmission electron microscopy, we show that the purified Cdc5p complex is a discrete structure [11].
• From these results, we conclude that multinucleate formation in response to Cdc5 overexpression is linked to titration of Swe1 function [20].

References