title: Plk1 phosphorylates Sgt1 at the kinetochores to promote timely kinetochore-microtubule attachment.
abstract: Accurate chromosome segregation during cell division maintains genomic integrity and requires the proper establishment of kinetochore-microtubule attachment in mitosis. As a key regulator of mitosis, Polo-like kinase 1 (Plk1) is essential for this attachment process, but the molecular mechanism remains elusive. Here we identify Sgt1, a cochaperone for Hsp90, as a novel Plk1 substrate during mitosis. We show that Sgt1 dynamically localizes at the kinetochores, which lack microtubule attachments during prometaphase. Plk1 is required for the kinetochore localization of Sgt1 and phosphorylates serine 331 of Sgt1 at the kinetochores. This phosphorylation event enhances the association of the Hsp90-Sgt1 chaperone with the MIS12 complex to stabilize this complex at the kinetochores and thus coordinates the recruitment of the NDC80 complex to form efficient microtubule-binding sites. Disruption of Sgt1 phosphorylation reduces the MIS12 and NDC80 complexes at the kinetochores, impairs stable microtubule attachment, and eventually results in chromosome misalignment to delay the anaphase onset. Our results demonstrate a mechanism for Plk1 in promoting kinetochore-microtubule attachment to ensure chromosome stability.
authors.affiliation: Department of Biochemistry, Purdue University, West Lafayette, IN, USA.
authors.forename: X Shawn
authors.initials: XS
authors.lastname: Liu
authors.forename: Bing
authors.initials: B
authors.lastname: Song
authors.forename: Jiabin
authors.initials: J
authors.lastname: Tang
authors.forename: Weiyi
authors.initials: W
authors.lastname: Liu
authors.forename: Shihuan
authors.initials: S
authors.lastname: Kuang
authors.forename: Xiaoqi
authors.initials: X
authors.lastname: Liu
mesh_terms: D018797:Cell Cycle Proteins / Q000032:analysis / Q000378:metabolism*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D018386:Kinetochores / Q000378:metabolism* / Q000648:ultrastructure; D008869:Microtubule-Associated Proteins / Q000032:analysis / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism* / Q000648:ultrastructure; D008938:Mitosis; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000032:analysis / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D000097869:Polo-Like Kinase 1
chemical_list: D018797:Cell Cycle Proteins; D008869:Microtubule-Associated Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D012694:Serine; D000097869:Polo-Like Kinase 1; C492664:MIS12 protein, human; C490164:SUGT1 protein, human