title: Pregnenolone functions in centriole cohesion during mitosis.
abstract: Cell division is controlled by a multitude of protein enzymes, but little is known about roles of metabolites in this mechanism. Here, we show that pregnenolone (P5), a steroid that is produced from cholesterol by the steroidogenic enzyme Cyp11a1, has an essential role in centriole cohesion during mitosis. During prometa-metaphase, P5 is accumulated around the spindle poles. Depletion of P5 induces multipolar spindles that result from premature centriole disengagement, which are rescued by ectopic introduction of P5, but not its downstream metabolites, into the cells. Premature centriole disengagement, induced by loss of P5, is not a result of precocious activation of separase, a key factor for the centriole disengagement in anaphase. Rather, P5 directly binds to the N-terminal coiled-coil domain of short-form of shugoshin 1 (sSgo1), a protector for centriole cohesion and recruits it to spindle poles in mitosis. Our results thus reveal a steroid-mediated centriole protection mechanism.
authors.affiliation: Department of Cell Biology, Institute for Virus Research, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan; Department of Cell and Developmental Biology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Hamasaki
authors.affiliation: Department of Cell Biology, Institute for Virus Research, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan; Department of Cell and Developmental Biology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Matsumura
authors.affiliation: Department of Molecular and Cellular BioAnalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Ayaka
authors.initials: A
authors.lastname: Satou
authors.affiliation: Department of Molecular and Cellular BioAnalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Chisato
authors.initials: C
authors.lastname: Takahashi
authors.affiliation: Department of Cell Biology, Institute for Virus Research, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan; Department of Cell and Developmental Biology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan.
authors.forename: Yukako
authors.initials: Y
authors.lastname: Oda
authors.affiliation: Department of Cell Biology, Institute for Virus Research, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan; Department of Cell and Developmental Biology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan.
authors.forename: Chika
authors.initials: C
authors.lastname: Higashiura
authors.affiliation: Department of Molecular and Cellular BioAnalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Ishihama
authors.affiliation: Department of Cell Biology, Institute for Virus Research, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan; Department of Cell and Developmental Biology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan. Electronic address: ftoyoshi@virus.kyoto-u.ac.jp.
authors.forename: Fumiko
authors.initials: F
authors.lastname: Toyoshima
mesh_terms: D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D002460:Cell Line; D002502:Centrioles / Q000187:drug effects / Q000378:metabolism*; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000172:deficiency / Q000235:genetics; D006801:Humans; D008938:Mitosis / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D011284:Pregnenolone / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D021381:Protein Transport / Q000187:drug effects; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors; D000097869:Polo-Like Kinase 1
chemical_list: D018797:Cell Cycle Proteins; D002786:Cholesterol Side-Chain Cleavage Enzyme; D011284:Pregnenolone; D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D000097869:Polo-Like Kinase 1; C496644:SGO1 protein, human