title: HILI destabilizes microtubules by suppressing phosphorylation and Gigaxonin-mediated degradation of TBCB.
abstract: Human PIWIL2, aka HILI, is a member of PIWI protein family and overexpresses in various tumors. However, the underlying mechanisms of HILI in tumorigenesis remain largely unknown. TBCB has a critical role in regulating microtubule dynamics and is overexpressed in many cancers. Here we report that HILI inhibits Gigaxonin-mediated TBCB ubiquitination and degradation by interacting with TBCB, promoting the binding between HSP90 and TBCB, and suppressing the interaction between Gigaxonin and TBCB. Meanwhile, HILI can also reduce phosphorylation level of TBCB induced by PAK1. Our results showed that HILI suppresses microtubule polymerization and promotes cell proliferation, migration and invasion via TBCB for the first time, revealing a novel mechanism for HILI in tumorigenesis.
authors.affiliation: Department of Medical genetics, State Key Laboratory of Biotherapy, West china Hospital, Sichuan University, Chengdu, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Tan
authors.affiliation: Department of Medical genetics, State Key Laboratory of Biotherapy, West china Hospital, Sichuan University, Chengdu, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Liao
authors.affiliation: Department of Medical genetics, State Key Laboratory of Biotherapy, West china Hospital, Sichuan University, Chengdu, China.
authors.forename: Lianfang
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Medical genetics, State Key Laboratory of Biotherapy, West china Hospital, Sichuan University, Chengdu, China.
authors.forename: Yilu
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Medical genetics, State Key Laboratory of Biotherapy, West china Hospital, Sichuan University, Chengdu, China.
authors.forename: Siyuan
authors.initials: S
authors.lastname: Jiang
authors.affiliation: Department of Medical genetics, State Key Laboratory of Biotherapy, West china Hospital, Sichuan University, Chengdu, China.
authors.forename: Dachang
authors.initials: D
authors.lastname: Tao
authors.affiliation: Department of Medical genetics, State Key Laboratory of Biotherapy, West china Hospital, Sichuan University, Chengdu, China.
authors.forename: Yunqiang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Medical genetics, State Key Laboratory of Biotherapy, West china Hospital, Sichuan University, Chengdu, China.
authors.forename: Yongxin
authors.initials: Y
authors.lastname: Ma
mesh_terms: D060565:Argonaute Proteins / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation / Q000502:physiology*; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D059748:Proteolysis; D014404:Tubulin / Q000378:metabolism
chemical_list: D060565:Argonaute Proteins; D003598:Cytoskeletal Proteins; C416508:GAN protein, human; D018841:HSP90 Heat-Shock Proteins; D008869:Microtubule-Associated Proteins; C486868:PIWIL2 protein, human; D014404:Tubulin; C501073:tubulin cofactor B, human