title: JMJD5 (Jumonji Domain-containing 5) Associates with Spindle Microtubules and Is Required for Proper Mitosis.
abstract: Precise mitotic spindle assembly is a guarantee of proper chromosome segregation during mitosis. Chromosome instability caused by disturbed mitosis is one of the major features of various types of cancer. JMJD5 has been reported to be involved in epigenetic regulation of gene expression in the nucleus, but little is known about its function in mitotic process. Here we report the unexpected localization and function of JMJD5 in mitotic progression. JMJD5 partially accumulates on mitotic spindles during mitosis, and depletion of JMJD5 results in significant mitotic arrest, spindle assembly defects, and sustained activation of the spindle assembly checkpoint (SAC). Inactivating SAC can efficiently reverse the mitotic arrest caused by JMJD5 depletion. Moreover, JMJD5 is found to interact with tubulin proteins and associate with microtubules during mitosis. JMJD5-depleted cells show a significant reduction of α-tubulin acetylation level on mitotic spindles and fail to generate enough interkinetochore tension to satisfy the SAC. Further, JMJD5 depletion also increases the susceptibility of HeLa cells to the antimicrotubule agent. Taken together, these results suggest that JMJD5 plays an important role in regulating mitotic progression, probably by modulating the stability of spindle microtubules.
authors.affiliation: From the Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China and.
authors.forename: Zhimin
authors.initials: Z
authors.lastname: He
authors.affiliation: From the Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China and.
authors.forename: Junyu
authors.initials: J
authors.lastname: Wu
authors.affiliation: From the Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China and.
authors.forename: Xiaonan
authors.initials: X
authors.lastname: Su
authors.affiliation: From the Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China and.
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: From the Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China and.
authors.forename: Lixia
authors.initials: L
authors.lastname: Pan
authors.affiliation: Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200092/200120, China.
authors.forename: Huimin
authors.initials: H
authors.lastname: Wei
authors.affiliation: Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200092/200120, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Fang
authors.affiliation: From the Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China and.
authors.forename: Haitao
authors.initials: H
authors.lastname: Li
authors.affiliation: From the Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China and wangdaliang@mail.tsinghua.edu.cn.
authors.forename: Da-Liang
authors.initials: DL
authors.lastname: Wang
authors.affiliation: From the Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China and Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200092/200120, China sfl@tongji.edu.cn.
authors.forename: Fang-Lin
authors.initials: FL
authors.lastname: Sun
mesh_terms: D000107:Acetylation / Q000187:drug effects; D019943:Amino Acid Substitution; D004351:Drug Resistance; D006367:HeLa Cells; D056466:Histone Demethylases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects; D008856:Microscopy, Fluorescence; D008870:Microtubules / Q000378:metabolism; D008938:Mitosis / Q000187:drug effects; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D055550:Protein Stability; D034622:RNA Interference; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D008941:Spindle Apparatus / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D059008:Time-Lapse Imaging; D014404:Tubulin / Q000378:metabolism; D050257:Tubulin Modulators / Q000494:pharmacology
chemical_list: D008164:Luminescent Proteins; D011993:Recombinant Fusion Proteins; D014404:Tubulin; D050257:Tubulin Modulators; D056466:Histone Demethylases; C570692:Jmjd5 protein, mouse; D056484:Jumonji Domain-Containing Histone Demethylases; C550342:KDM8 protein, human
keywords: JMJD5; cell biology; cell division; microtubule; mitosis; mitotic spindle; α-tubulin acetylation