APC/C-Cdh1-mediated degradation of the Polo kinase Cdc5 promotes the return of Cdc14 into the nucleolus.
In the budding yeast Saccharomyces cerevisiae, the protein phosphatase Cdc14 triggers exit from mitosis by promoting the inactivation of cyclin-dependent kinases (CDKs). Cdc14's activity is controlled by Cfi1/Net1, which holds and inhibits the phosphatase in the nucleolus from G1 until metaphase. During anaphase, two regulatory networks, the Cdc14 Early Anaphase Release (FEAR) network and the Mitotic Exit Network (MEN), promote the dissociation of Cdc14 from its inhibitor, allowing the phosphatase to reach its targets throughout the cell. The molecular circuits that trigger the return of Cdc14 into the nucleolus after the completion of exit from mitosis are not known. Here we show that activation of a ubiquitin ligase known as the Anaphase-Promoting Complex or Cyclosome (APC/C) bound to the specificity factor Cdh1 triggers the degradation of the Polo kinase Cdc5, a key factor in releasing Cdc14 from its inhibitor in the nucleolus.
Visintin
Clara
C
Department of Experimental Oncology, European Institute of Oncology, Milano 20141, Italy.
Tomson
Brett N
BN
Rahal
Rami
R
Paulson
Jennifer
J
Cohen
Michael
M
Taunton
Jack
J
Amon
Angelika
A
Visintin
Rosella
R
D000483:Alleles; D064173:Anaphase-Promoting Complex-Cyclosome; D064200:Cdh1 Proteins; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002466:Cell Nucleolus / Q000201:enzymology*; D010450:Endopeptidases / Q000378:metabolism; D008677:Metaphase; D008856:Microscopy, Fluorescence; D008938:Mitosis; D008954:Models, Biological; D009687:Nuclear Proteins; D014176:Protein Biosynthesis; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D064247:Separase; D043743:Ubiquitin-Protein Ligase Complexes / Q000378:metabolism*
C074860:CDC14 protein, S cerevisiae; C577583:CDH1 protein, S cerevisiae; D064200:Cdh1 Proteins; D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; C416648:SPO12 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; C081927:CDC5 protein, S cerevisiae; D017027:Protein Tyrosine Phosphatases; D010450:Endopeptidases; D064247:Separase