title: Tex14, a Plk1-regulated protein, is required for kinetochore-microtubule attachment and regulation of the spindle assembly checkpoint.
abstract: Proper assembly of kinetochores (KTs) during mitosis is required for bipolar attachment of spindle microtubules (MTs) and the accumulation of spindle assembly checkpoint (SAC) components. Here we show that testis-expressed protein 14 (Tex14), which has been implicated in midbody function, is recruited to KTs by Plk1 in a Cdk1-dependent manner during early mitosis. Exclusion of Tex14 from kinetochores results in an inability to efficiently localize outer KT components, impaired KT-MT attachment, chromosome congression defects, and whole-chromosome instability. In addition, we demonstrate that phosphorylation of Tex14 by Plk1 during metaphase promotes APC(Cdc20)-mediated Tex14 degradation. Inhibition of this phosphorylation event causes retention of Tex14 at KTs and results in delayed metaphase-to-anaphase transition and chromosome segregation defects. Our findings identify Tex14 as an important mediator of KT structure and function and the fidelity of chromosome separation.
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Gourish
authors.initials: G
authors.lastname: Mondal
authors.forename: Akihiro
authors.initials: A
authors.lastname: Ohashi
authors.forename: Lin
authors.initials: L
authors.lastname: Yang
authors.forename: Matthew
authors.initials: M
authors.lastname: Rowley
authors.forename: Fergus J
authors.initials: FJ
authors.lastname: Couch
mesh_terms: D001665:Binding Sites; D016203:CDC2 Protein Kinase / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D020090:Chromosome Segregation; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D018386:Kinetochores / Q000378:metabolism* / Q000648:ultrastructure; D059566:M Phase Cell Cycle Checkpoints; D008870:Microtubules / Q000378:metabolism* / Q000648:ultrastructure; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D000097869:Polo-Like Kinase 1
chemical_list: D016203:CDC2 Protein Kinase; D018797:Cell Cycle Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D000097869:Polo-Like Kinase 1; C548797:TEX14 protein, human