title: The Giardia cell cycle progresses independently of the anaphase-promoting complex.
abstract: Most cell cycle regulation research has been conducted in model organisms representing a very small part of the eukaryotic domain. The highly divergent human pathogen Giardia intestinalis is ideal for studying the conservation of eukaryotic pathways. Although Giardia has many cell cycle regulatory components, its genome lacks all anaphase-promoting complex (APC) components. In the present study, we show that a single mitotic cyclin in Giardia is essential for progression into mitosis. Strikingly, Giardia cyclin B lacks the conserved N-terminal motif required for timely degradation mediated by the APC and ubiquitin conjugation. Expression of Giardia cyclin B in fission yeast is toxic, leading to a prophase arrest, and this toxicity is suppressed by the addition of a fission yeast degradation motif. Cyclin B is degraded during mitosis in Giardia cells, but this degradation appears to be independent of the ubiquitination pathway. Other putative APC substrates, aurora and polo-like kinases, also show no evidence of ubiquitination. This is the first example of mitosis not regulated by the APC and might reflect an evolutionary ancient form of cell cycle regulation.
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA. stephane.gourguechon@berkeley.edu
authors.forename: Stéphane
authors.initials: S
authors.lastname: Gourguechon
authors.forename: Liam J
authors.initials: LJ
authors.lastname: Holt
authors.forename: W Zacheus
authors.initials: WZ
authors.lastname: Cande
mesh_terms: D064173:Anaphase-Promoting Complex-Cyclosome / Q000235:genetics; D005075:Biological Evolution; D002453:Cell Cycle / Q000235:genetics; D017124:Conserved Sequence / Q000235:genetics; D019926:Cyclin B / Q000235:genetics / Q000378:metabolism*; D016829:Giardia lamblia / Q000502:physiology*; D060172:Morpholinos / Q000235:genetics; D010766:Phosphorylation; D017434:Protein Structure, Tertiary / Q000235:genetics; D059748:Proteolysis; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*; D012568:Schizosaccharomyces; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*; D013045:Species Specificity; D054875:Ubiquitination
chemical_list: D019926:Cyclin B; D060172:Morpholinos; D015800:Protozoan Proteins; D029702:Schizosaccharomyces pombe Proteins; D064173:Anaphase-Promoting Complex-Cyclosome
keywords: APC; Anaphase-promoting complex; Calyculin A; Cyclin B; Giardia; Mitosis; Staurosporine