Clathrin recruits phosphorylated TACC3 to spindle poles for bipolar spindle assembly and chromosome alignment

Fu, Wenxiang; Tao, Wei; Zheng, Puwei; Fu, Jingyan; Bian, Minglei; Jiang, Qing; Clarke, Paul R.; Zhang, Chuanmao

doi:10.1242/jcs.075911

Cited by 66 publications

(142 citation statements)

References 27 publications

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“…Aurora-A has been shown to phosphorylate TACC3 WT at S552 and S558 which is required for the localization of a TACC3-chTOG-clathrin complex to mitotic spindle microtubules and spindle poles (7,18,45). Localization of TACC3 to kinetochore fibers in complex with chTOG and clathrin is believed to assist with stabilization and formation of the mitotic spindle (45).…”

Section: Discussionmentioning

confidence: 99%

“…This domain is believed to play an important role in localization of the protein during mitosis (4). Although TACC2 has been shown to be dispensable for normal mouse development without affecting proliferation, cell-cycle progression, or centrosome numbers (5), in contrast, knockdown of TACC3 has been shown to result in G 2 -M phase arrest, apoptosis, abnormal spindle assembly, chromosome misalignment, and impaired microtubule assembly and nucleation (6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

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Oncogenic Gene Fusion FGFR3-TACC3 Is Regulated by Tyrosine Phosphorylation

Nelson

Meyer

Siari

et al. 2016

Molecular Cancer Research

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Fibroblast growth factor receptors (FGFR) are critical for cell proliferation and differentiation. Mutation and/or translocation of FGFRs lead to aberrant signaling that often results in developmental syndromes or cancer growth. As sequencing of human tumors becomes more frequent, so does the detection of FGFR translocations and fusion proteins. The research conducted in this article examines a frequently identified fusion protein between FGFR3 and transforming acidic coiled-coil containing protein 3 (TACC3), frequently identified in glioblastoma, lung cancer, bladder cancer, oral cancer, head and neck squamous cell carcinoma, gallbladder cancer, and cervical cancer. Using titanium dioxide-based phosphopeptide enrichment (TiO 2 )-liquid chromatography (LC)-high mass accuracy tandem mass spectrometry (MS/MS), it was demonstrated that the fused coiled-coil TACC3 domain results in constitutive phosphorylation of key activating FGFR3 tyrosine residues. The presence of the TACC coiled-coil domain leads to increased and altered levels of FGFR3 activation, fusion protein phosphorylation, MAPK pathway activation, nuclear localization, cellular transformation, and IL3-independent proliferation. Introduction of K508R FGFR3 kinase-dead mutation abrogates these effects, except for nuclear localization which is due solely to the TACC3 domain.Implications: These results demonstrate that FGFR3 kinase activity is essential for the oncogenic effects of the FGFR3-TACC3 fusion protein and could serve as a therapeutic target, but that phosphorylated tyrosine residues within the TACC3-derived portion are not critical for activity.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Oncogenic Gene Fusion FGFR3-TACC3 Is Regulated by Tyrosine Phosphorylation

Nelson

Meyer

Siari

et al. 2016

Molecular Cancer Research

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“…Recently, several groups found that clathrin regulates spindle assembly by targeting TACC3 to the spindles ( Figure 1A) [15][16][17]. During mitosis, Aurora A phosphorylates TACC3 and this phosphorylation ensures TACC3 to localize to the spindles in Drosophila, Xenopus and human [21][22][23][24][25].…”

Section: Clathrin and Mitotic Spindle Assemblymentioning

confidence: 98%

“…More recently, the role of clathrin in mitosis has been widely recognized. Several individual groups including ours have shed novel lights on the function of clathrin in mitosis at the molecular level [15][16][17][18]. These studies demonstrated that clathrin forms a complex with TACC3 to regulate spindle assembly and chromosome alignment.…”

mentioning

confidence: 90%

“…The road leading to discovery of the novel function of clathrin in mitosis started from exploring how phosphorylation-catalyzed TACC3 affects mitotic spindle assembly. By mass spectrometry analysis, clathrin was initially identified as one of the specific binding partners of phosphorylated TACC3 [15][16][17]. Through site-directed mutagenesis studies joining with biochemical and cell biological assays, it was demonstrated that the binding of CHC and phosphorylated TACC3 is required for proper mitotic spindle assembly.…”

Section: Clathrin and Mitotic Spindle Assemblymentioning

confidence: 99%

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Novel functions of endocytic player clathrin in mitosis

Jiang

Zhang

2011

Cell Res

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Clathrin has been widely recognized as a pivotal player in endocytosis, in which several adaptors and accessory proteins are involved. Recent studies suggested that clathrin is also essential for cell division. Here this review mainly focuses on the clathrin-dependent mechanisms involved in spindle assembly and chromosome alignment. In mitosis, clathrin forms a complex with phosphorylated TACC3 to ensure spindle stability and proper chromosome alignment. The clathrin-regulated mechanism in mitosis requires the crosstalk among clathrin, spindle assembly factors (SAFs), Ran-GTP and mitotic kinases. Meanwhile, a coordinated mechanism is required for role transitions of clathrin during endocytosis and mitosis. Taken together, the findings of the multiple functions of clathrin besides endocytosis have expanded our understanding of the basic cellular activities.

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Mitotic Spindle Assembly: The Roles of Microtubule Nucleation and Assembly

Luo

Jiang

et al. 2016

Encyclopedia of Life Sciences

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In all eukaryotes, the assembly of a bipolar mitotic spindle requires highly ordered arrangement of microtubule arrays. This process is facilitated by the formation of new microtubules and involves many proteins that regulate microtubule organisation and dynamics. While the γ‐tubulin ring complex ( γTuRC ) determines the spatial and temporal control over the initiation of microtubule growth, recent work reveals the molecular mechanisms behind these dynamic events. Key Concepts Mitotic spindle is a macromolecular temporary machine that initially assembles in early mitosis and disappears at the end of mitosis. Mitotic spindle mainly consists of microtubules with a variety of microtubule‐associated proteins (MAPs) and motor proteins. Microtubules are assembled from α/β‐tubulin heterodimers that contact both in longitudinal and lateral directions. The MAPs and motor proteins take responsibility for regulating the growth or shrinkage of the microtubules. Microtubule nucleation occurs at microtubule‐organising centres (MTOCs). γ‐Tubulin and several other components assemble into γ‐tubulin ring complex (γTuRC) that determines when and where to nucleate the microtubule. Diffusible RanGTP gradient from chromosomes facilitates chromosome‐mediated microtubule nucleation and assembly. Microtubules may serve as nucleation sites for microtubule nucleation and assembly regulated by γTuRC and augmin protein complex. Small microtubule seed/aster formation and sorting facilitate kinetochore capture by microtubules and mitotic spindle assembly. Mitotic kinases such as cyclin‐dependent kinases, auroras and Plks regulate microtubule nucleation and assembly during mitotic spindle formation.

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Clathrin recruits phosphorylated TACC3 to spindle poles for bipolar spindle assembly and chromosome alignment

Cited by 66 publications

References 27 publications

Oncogenic Gene Fusion FGFR3-TACC3 Is Regulated by Tyrosine Phosphorylation

Oncogenic Gene Fusion FGFR3-TACC3 Is Regulated by Tyrosine Phosphorylation

Novel functions of endocytic player clathrin in mitosis

Mitotic Spindle Assembly: The Roles of Microtubule Nucleation and Assembly

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