title: Cell-cycle-regulated expression of STIL controls centriole number in human cells.
abstract: Control of centriole number is crucial for genome stability and ciliogenesis. Here, we characterize the role of human STIL, a protein that displays distant sequence similarity to the centriole duplication factors Ana2 in Drosophila and SAS-5 in Caenorhabditis elegans. Using RNA interference, we show that STIL is required for centriole duplication in human cells. Conversely, overexpression of STIL triggers the near-simultaneous formation of multiple daughter centrioles surrounding each mother, which is highly reminiscent of the phenotype produced by overexpression of the polo-like kinase PLK4 or the spindle assembly abnormal protein 6 homolog (SAS-6). We further show, by fluorescence and immunoelectron microscopy, that STIL is recruited to nascent daughter centrioles at the onset of centriole duplication and degraded, in an APC/C(Cdc20-Cdh1)-dependent manner, upon passage through mitosis. We did not detect a stable complex between STIL and SAS-6, but the two proteins resemble each other with regard to both localization and cell cycle control of expression. Thus, STIL cooperates with SAS-6 and PLK4 in the control of centriole number and represents a key centriole duplication factor in human cells.
authors.affiliation: Biozentrum, University of Basel, Klingelbergstr. 50/70, CH-4056 Basel,  Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Arquint
authors.forename: Katharina F
authors.initials: KF
authors.lastname: Sonnen
authors.forename: York-Dieter
authors.initials: YD
authors.lastname: Stierhof
authors.forename: Erich A
authors.initials: EA
authors.lastname: Nigg
mesh_terms: D000595:Amino Acid Sequence; D015703:Antigens, CD; D015820:Cadherins / Q000235:genetics; D064199:Cdc20 Proteins; D002453:Cell Cycle / Q000502:physiology; D059447:Cell Cycle Checkpoints; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division / Q000502:physiology*; D002460:Cell Line; D002502:Centrioles / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000378:metabolism; D011506:Proteins / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering; D016415:Sequence Alignment
chemical_list: D015703:Antigens, CD; C424522:BTG3 protein, human; C513384:CDH1 protein, human; D015820:Cadherins; D064199:Cdc20 Proteins; D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D034741:RNA, Small Interfering; C497202:SASS6 protein, human; C071236:STIL protein, human; C577488:CDC20 protein, human; C490219:PLK4 protein, human; D017346:Protein Serine-Threonine Kinases