title: STIL is required for centriole duplication in human cells.
abstract: Centrioles are key structural elements of centrosomes and primary cilia. In mammals, only a few proteins including PLK4, CPAP (CENPJ), SAS6, CEP192, CEP152 and CEP135 have thus far been identified to be required for centriole duplication. STIL (SCL/TAL1 interrupting locus, also known as SIL) is a centrosomal protein that is essential for mouse and zebrafish embryonic development and mutated in primary microcephaly. Here, we show that STIL localizes to the pericentriolar material surrounding parental centrioles. Its overexpression results in excess centriole formation. siRNA-mediated depletion of STIL leads to loss of centrioles and abrogates PLK4-induced centriole overduplication. Additionally, we show that STIL is necessary for SAS6 recruitment to centrioles, suggesting that it is essential for daughter centriole formation, interacts with the centromere protein CPAP and rapidly shuttles between the cytoplasm and centrioles. Consistent with the requirement of centrioles for cilia formation, Stil(-/-) mouse embryonic fibroblasts lack primary cilia--a phenotype that can be reverted by restoration of STIL expression. These findings demonstrate that STIL is an essential component of the centriole replication machinery in mammalian cells.
authors.affiliation: Clinical Cooperation Unit Molecular Hematology/Oncology, German Cancer Research Center (DKFZ) and Dept. of Internal Medicine V, University of Heidelberg, 69120 Heidelberg,  Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Vulprecht
authors.forename: Ahuvit
authors.initials: A
authors.lastname: David
authors.forename: Alexandra
authors.initials: A
authors.lastname: Tibelius
authors.forename: Asher
authors.initials: A
authors.lastname: Castiel
authors.forename: Gleb
authors.initials: G
authors.lastname: Konotop
authors.forename: Fengying
authors.initials: F
authors.lastname: Liu
authors.forename: Felix
authors.initials: F
authors.lastname: Bestvater
authors.forename: Marc S
authors.initials: MS
authors.lastname: Raab
authors.forename: Hanswalter
authors.initials: H
authors.lastname: Zentgraf
authors.forename: Shai
authors.initials: S
authors.lastname: Izraeli
authors.forename: Alwin
authors.initials: A
authors.lastname: Krämer
mesh_terms: D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002455:Cell Division / Q000502:physiology; D002460:Cell Line; D002502:Centrioles / Q000235:genetics / Q000378:metabolism*; D018385:Centrosome / Q000502:physiology; D002923:Cilia / Q000378:metabolism*; D003593:Cytoplasm / Q000502:physiology; D057809:HEK293 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering
chemical_list: C414735:CENPJ protein, human; D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008869:Microtubule-Associated Proteins; D034741:RNA, Small Interfering; C497202:SASS6 protein, human; C071236:STIL protein, human; C490219:PLK4 protein, human; D017346:Protein Serine-Threonine Kinases