title: Acm1 contributes to nuclear positioning by inhibiting Cdh1-substrate interactions.
abstract: The anaphase-promoting complex (APC) is tightly regulated during cell division, often by pseudosubstrate binding to its coactivators Cdh1 and Cdc20. Budding yeast Acm1 is a Cdh1 pseudosubstrate inhibitor whose biological function is unknown. We show here that cells lacking Acm1 have defects in nuclear positioning and spindle morphology during mitosis. However, Cdh1 substrates are not destabilized in the absence of Acm1 and expression of inactive Cdh1 mutants that retain substrate binding is sufficient for the acm1 phenotype. We conclude that Acm1 is not required to inhibit APC(Cdh1) activity but rather prevents untimely Cdh1-substrate interactions. We further provide evidence suggesting that the substrate primarily responsible for the acm1 phenotype is the bud neck-localized kinase, Hsl1. Our results imply that at least some coactivator-substrate interactions require regulation. Several unrelated APC pseudosubstrates have been identified in diverse eukaryotes and their ability to simultaneously inhibit enzymatic activity and substrate binding may partly explain why this regulatory mechanism has been selected repeatedly during evolution.
authors.affiliation: Department of Biochemistry and Center for Cancer Research, Purdue University, West Lafayette, IN, USA.
authors.forename: Juan S
authors.initials: JS
authors.lastname: Martinez
authors.forename: Hana
authors.initials: H
authors.lastname: Hall
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Bartolowits
authors.forename: Mark C
authors.initials: MC
authors.lastname: Hall
mesh_terms: D064173:Anaphase-Promoting Complex-Cyclosome; D064200:Cdh1 Proteins; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D034281:Dynamins / Q000235:genetics; D055786:Gene Knockout Techniques; D008938:Mitosis; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D016196:S Phase; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D008941:Spindle Apparatus / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism; D043743:Ubiquitin-Protein Ligase Complexes / Q000378:metabolism
chemical_list: C516306:Acm1 protein, S cerevisiae; C577583:CDH1 protein, S cerevisiae; D064200:Cdh1 Proteins; D018797:Cell Cycle Proteins; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D014404:Tubulin; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; C106494:HSL1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; D034281:Dynamins