title: Phosphorylation and dephosphorylation regulate APC/C(Cdh1) substrate degradation.
abstract: The Anaphase Promoting Complex/Cyclosome (APC/C) ubiquitin ligase activated by its G1 specific adaptor protein Cdh1 is a major regulator of the cell cycle. The APC/C(Cdh1) mediates degradation of dozens of proteins, however, the kinetics and requirements for their degradation are largely unknown. We demonstrate that overexpression of the constitutive active CDH1(m11) mutant that is not inhibited by phosphorylation results in mitotic exit in the absence of the FEAR and MEN pathways, and DNA re-replication in the absence of Cdc7 activity. This mode of mitotic exit also reveals additional requirements for APC/C(Cdh1) substrate degradation, which for some substrates such as Pds1 or Clb5 is dephosphorylation, but for others such as Cdc5 is phosphorylation.
authors.affiliation: a The Department of Genetics ; The Alexander Silberman Institute of Life Sciences; The Hebrew University of Jerusalem ; Jerusalem , Israel.
authors.forename: Kobi J
authors.initials: KJ
authors.lastname: Simpson-Lavy
authors.affiliation: a The Department of Genetics ; The Alexander Silberman Institute of Life Sciences; The Hebrew University of Jerusalem ; Jerusalem , Israel.
authors.forename: Drora
authors.initials: D
authors.lastname: Zenvirth
authors.affiliation: a The Department of Genetics ; The Alexander Silberman Institute of Life Sciences; The Hebrew University of Jerusalem ; Jerusalem , Israel.
authors.forename: Michael
authors.initials: M
authors.lastname: Brandeis
mesh_terms: D064173:Anaphase-Promoting Complex-Cyclosome / Q000235:genetics / Q000378:metabolism*; D064200:Cdh1 Proteins / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D019926:Cyclin B / Q000235:genetics / Q000378:metabolism; D004261:DNA Replication / Q000235:genetics / Q000502:physiology; D008938:Mitosis / Q000235:genetics / Q000502:physiology; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C577583:CDH1 protein, S cerevisiae; C076558:CLB5 protein, S cerevisiae; D064200:Cdh1 Proteins; D018797:Cell Cycle Proteins; D019926:Cyclin B; C088096:Dbf4 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D064173:Anaphase-Promoting Complex-Cyclosome; D017346:Protein Serine-Threonine Kinases; C081927:CDC5 protein, S cerevisiae
keywords: APC/C, Cdc5, Cdc14, Cdh1, Clb5, Dbf4, DNA replication, exit from mitosis, Pds1, substrate phosphorylation, yeast