title: Phosphorylation of Ataxin-10 by polo-like kinase 1 is required for cytokinesis.
abstract: Spinocerebellar ataxia type 10 (SCA10) is an autosomal dominant neurologic disorder, whose symptoms include cerebellar ataxia and epilepsy. The disease is caused by ATTCT expansion in the ATXN10 gene, which encodes the Ataxin-10 protein. Here we identified polo-like kinase 1 (Plk1) as one of Ataxin-10's binding partners. We show that epitope-tagged Ataxin-10 and Plk1 coimmunoprecipitate, and Plk1 phosphorylates Ataxin-10 at S77 and T82 in vitro. Knockdown of ATXN10 with siRNA in HeLa cells results in cytokinesis defects-multinucleation, which are rescued by wild-type Ataxin-10, but not the phosphor-deficient 2A mutant. Phosphorylation-specific antibodies towards pS77 detect specific signals at the midbody. Like the knockdown, overexpression of the 2A mutant generates multinucleated cells and the 2A mutant shows decreased interaction with the Plk1 polo-box domain. In addition, we found that Ataxin-10 is ubiquitinated, and is subject to proteasome-dependent degradation, which is delayed in the 2A mutant. We propose a model in which Plk1 phosphorylation of Ataxin-10 influences its degradation and cytokinesis, which may provide mechanistic insight to SCA10's pathogenesis.
authors.affiliation: Laboratory of Cancer Biology, College of Life Sciences, Capital Normal University, Beijing, China. jing_li@mail.cnu.edu.cn
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Jue
authors.initials: J
authors.lastname: Wang
authors.forename: Wenya
authors.initials: W
authors.lastname: Hou
authors.forename: Zhiyi
authors.initials: Z
authors.lastname: Jing
authors.forename: Chuan
authors.initials: C
authors.lastname: Tian
authors.forename: Yi
authors.initials: Y
authors.lastname: Han
authors.forename: Ji
authors.initials: J
authors.lastname: Liao
authors.forename: Meng-Qiu
authors.initials: MQ
authors.lastname: Dong
authors.forename: Xingzhi
authors.initials: X
authors.lastname: Xu
mesh_terms: D000067736:Ataxin-10; D001665:Binding Sites; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D048749:Cytokinesis; D055785:Gene Knockdown Techniques; D015726:Giant Cells / Q000166:cytology / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010766:Phosphorylation; D054730:Protein Interaction Domains and Motifs; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D055550:Protein Stability; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011621:Pteridines / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction; D013912:Threonine / Q000378:metabolism; D014162:Transfection; D054875:Ubiquitination; D000097869:Polo-Like Kinase 1
chemical_list: D000067736:Ataxin-10; D018797:Cell Cycle Proteins; D009419:Nerve Tissue Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D011621:Pteridines; D034741:RNA, Small Interfering; D012694:Serine; D013912:Threonine; D000097869:Polo-Like Kinase 1; C503889:ATXN10 protein, human; C518477:BI 2536