title: APC16 is a conserved subunit of the anaphase-promoting complex/cyclosome.
abstract: Error-free chromosome segregation depends on timely activation of the multi-subunit E3 ubiquitin ligase APC/C. Activation of the APC/C initiates chromosome segregation and mitotic exit by targeting critical cell-cycle regulators for destruction. The APC/C is the principle target of the mitotic checkpoint, which prevents segregation while chromosomes are unattached to spindle microtubules. We now report the identification and characterization of APC16, a conserved subunit of the APC/C. APC16 was found in association with tandem-affinity-purified mitotic checkpoint complex protein complexes. APC16 is a bona fide subunit of human APC/C: it is present in APC/C complexes throughout the cell cycle, the phenotype of APC16-depleted cells copies depletion of other APC/C subunits, and APC16 is important for APC/C activity towards mitotic substrates. APC16 sequence homologues can be identified in metazoans, but not fungi, by four conserved primary sequence stretches. We provide evidence that the C. elegans gene K10D2.4 and the D. rerio gene zgc:110659 are functional equivalents of human APC16. Our findings show that APC/C is composed of previously undescribed subunits, and raise the question of why metazoan APC/C is molecularly different from unicellular APC/C.
authors.affiliation: Department of Physiological Chemistry and Cancer Genomics Centre, UMC Utrecht, Utrecht, The Netherlands. g.j.p.l.kops@umcutrecht.nl
authors.forename: Geert J P L
authors.initials: GJ
authors.lastname: Kops
authors.forename: Monique
authors.initials: M
authors.lastname: van der Voet
authors.forename: Moniek
authors.initials: M
authors.lastname: van der Voet
authors.forename: Michael S
authors.initials: MS
authors.lastname: Manak
authors.forename: Maria H J
authors.initials: MH
authors.lastname: van Osch
authors.forename: Said M
authors.initials: SM
authors.lastname: Naini
authors.forename: Andrea
authors.initials: A
authors.lastname: Brear
authors.forename: Ian X
authors.initials: IX
authors.lastname: McLeod
authors.forename: Dirk M
authors.initials: DM
authors.lastname: Hentschel
authors.forename: John R
authors.initials: JR
authors.lastname: Yates
authors.forename: Sander
authors.initials: S
authors.lastname: van den Heuvel
authors.forename: Jagesh V
authors.initials: JV
authors.lastname: Shah
mesh_terms: D064173:Anaphase-Promoting Complex-Cyclosome; D000818:Animals; D017173:Caenorhabditis elegans; D002135:Calcium-Binding Proteins / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D020090:Chromosome Segregation / Q000235:genetics; D017124:Conserved Sequence / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D064246:Mad2 Proteins; D008938:Mitosis; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D012097:Repressor Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D008941:Spindle Apparatus / Q000378:metabolism; D053719:Tandem Mass Spectrometry; D043743:Ubiquitin-Protein Ligase Complexes / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics* / Q000378:metabolism
chemical_list: D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; C577697:MAD2L1 protein, human; D064246:Mad2 Proteins; D021122:Protein Subunits; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; D044767:Ubiquitin-Protein Ligases; C090464:Bub1 spindle checkpoint protein; D017346:Protein Serine-Threonine Kinases
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