title: The STARD9/Kif16a kinesin associates with mitotic microtubules and regulates spindle pole assembly.
abstract: During cell division, cells form the microtubule-based mitotic spindle, a highly specialized and dynamic structure that mediates proper chromosome transmission to daughter cells. Cancer cells can show perturbed mitotic spindles and an approach in cancer treatment has been to trigger cell killing by targeting microtubule dynamics or spindle assembly. To identify and characterize proteins necessary for spindle assembly, and potential antimitotic targets, we performed a proteomic and genetic analysis of 592 mitotic microtubule copurifying proteins (MMCPs). Screening for regulators that affect both mitosis and apoptosis, we report the identification and characterization of STARD9, a kinesin-3 family member, which localizes to centrosomes and stabilizes the pericentriolar material (PCM). STARD9-depleted cells have fragmented PCM, form multipolar spindles, activate the spindle assembly checkpoint (SAC), arrest in mitosis, and undergo apoptosis. Interestingly, STARD9-depletion synergizes with the chemotherapeutic agent taxol to increase mitotic death, demonstrating that STARD9 is a mitotic kinesin and a potential antimitotic target.
authors.affiliation: Department of Pathology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, USA. torres@chem.ucla.edu
authors.forename: Jorge Z
authors.initials: JZ
authors.lastname: Torres
authors.forename: Matthew K
authors.initials: MK
authors.lastname: Summers
authors.forename: David
authors.initials: D
authors.lastname: Peterson
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Brauer
authors.forename: James
authors.initials: J
authors.lastname: Lee
authors.forename: Silvia
authors.initials: S
authors.lastname: Senese
authors.forename: Ankur A
authors.initials: AA
authors.lastname: Gholkar
authors.forename: Yu-Chen
authors.initials: YC
authors.lastname: Lo
authors.forename: Xingye
authors.initials: X
authors.lastname: Lei
authors.forename: Kenneth
authors.initials: K
authors.lastname: Jung
authors.forename: David C
authors.initials: DC
authors.lastname: Anderson
authors.forename: David P
authors.initials: DP
authors.lastname: Davis
authors.forename: Lisa
authors.initials: L
authors.lastname: Belmont
authors.forename: Peter K
authors.initials: PK
authors.lastname: Jackson
mesh_terms: D000595:Amino Acid Sequence; D017209:Apoptosis; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002502:Centrioles / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008868:Microtubule Proteins / Q000032:analysis*; D008870:Microtubules / Q000378:metabolism*; D008938:Mitosis; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology*; D010802:Phylogeny; D020543:Proteome / Q000032:analysis; D016415:Sequence Alignment; D008941:Spindle Apparatus
chemical_list: D002352:Carrier Proteins; D008868:Microtubule Proteins; D020543:Proteome; C515004:STARD9 protein, human