The Centrosomal Adaptor TACC3 and the Microtubule Polymerase chTOG Interact via Defined C-terminal Subdomains in an Aurora-A Kinase-independent Manner

Thakur, Harishchandra; Singh, Madhurendra; Nagel-Steger, Luitgard; Kremer, Jana; Prumbaum, Daniel; Fansa, Eyad K.; Ezzahoini, Hakima; Nouri, Kazem; Gremer, Lothar; Abts, André; Schmitt, Lutz; Raunser, Stefan; Ahmadian, Mohammad Réza; Piekorz, Roland P.

doi:10.1074/jbc.m113.532333

Cited by 41 publications

(39 citation statements)

References 82 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The weaker band size was indistinguishable from that of GFP‐NtermTACC1, suggesting in a small subset of protein, the C‐terminal TACC domain was cleaved off. It has been observed in mouse that the C‐terminal TACC domain could be cleaved from the rest of TACC3 using a thrombin cleavage site [Thakur et al, 2014]. This particular cleavage site is not present in Xenopus laevis TACC3 or TACC1, and it was noted by Thakur et al 2014 authors that it is unclear whether the thrombin cleavage site in mouse has any physiological relevance.…”

Section: Resultsmentioning

confidence: 99%

“…It has been observed in mouse that the C‐terminal TACC domain could be cleaved from the rest of TACC3 using a thrombin cleavage site [Thakur et al, 2014]. This particular cleavage site is not present in Xenopus laevis TACC3 or TACC1, and it was noted by Thakur et al 2014 authors that it is unclear whether the thrombin cleavage site in mouse has any physiological relevance. However, given that we observed a protein fragment that appears to result from the cleavage of the TACC domain in Xenopus TACC1 (Fig.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Xenopus TACC1 is a microtubule plus‐end tracking protein that can regulate microtubule dynamics during embryonic development

et al. 2015

View full text Add to dashboard Cite

Microtubule plus‐end dynamics are regulated by a family of proteins called plus‐end tracking proteins (+TIPs). We recently demonstrated that the transforming acidic coiled‐coil (TACC) domain family member, TACC3, can function as a +TIP to regulate microtubule dynamics in Xenopus laevis embryonic cells. Although it has been previously reported that TACC3 is the only TACC family member that exists in Xenopus, our examination of its genome determined that Xenopus, like all other vertebrates, contains three TACC family members. Here, we investigate the localization and function of Xenopus TACC1, the founding member of the TACC family. We demonstrate that it can act as a +TIP to regulate microtubule dynamics, and that the conserved C‐terminal TACC domain is required for its localization to plus‐ends. We also show that, in Xenopus embryonic mesenchymal cells, TACC1 and TACC3 are each required for maintaining normal microtubule growth speed but exhibit some functional redundancy in the regulation of microtubule growth lifetime. Given the conservation of TACC1 in Xenopus and other vertebrates, we propose that Xenopus laevis is a useful system to investigate unexplored cell biological functions of TACC1 and other TACC family members in the regulation of microtubule dynamics. © 2015 The Authors. Cytoskeleton, Published by Wiley Periodicals, Inc.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Xenopus TACC1 is a microtubule plus‐end tracking protein that can regulate microtubule dynamics during embryonic development

et al. 2015

View full text Add to dashboard Cite

show abstract

“…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%

“…1A, chosen due to the high occurrence of this particular fusion breakpoint (3,17). This fusion is predicted to contain the extracellular, transmembrane, and intracellular kinase domains of FGFR3 fused 5 0 to the coiled-coil domain of TACC3 (18). Constitutively activated FGFR3 clones were produced by the K650E mutation.…”

Section: Constitutive Phosphorylation Of Fgfr3-tacc3 Fusion Proteinmentioning

confidence: 99%

Oncogenic Gene Fusion FGFR3-TACC3 Is Regulated by Tyrosine Phosphorylation

Nelson

Meyer

Siari

et al. 2016

Molecular Cancer Research

View full text Add to dashboard Cite

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.

show abstract

“…chTOG is recruited to this complex via its interaction with TACC3. Previous work has shown chTOG 1517-1957 is sufficient for binding to TACC3 (Hood et al 2013;Thakur et al 2014). We characterized the equivalent region in MSPS (residues 1591-1941) by NMR spectroscopy.…”

Section: Biological Contextmentioning

confidence: 99%

Solution NMR assignment of the cryptic sixth TOG domain of mini spindles

2015

View full text Add to dashboard Cite

TOG domains contribute to the organisation of microtubules through their ability to bind tubulin. They are found in members of the XMAP215 family of proteins, which act as microtubule polymerases and fulfill important roles in the formation of the mitotic spindle and in the assembly of kinetochore fibres. We recently identified a cryptic TOG domain in the XMAP215 family proteins, chTOG and its Drosophila homologue, mini spindles. This domain is not part of the well-established array of TOG domains involved in tubulin polymerisation. Instead it forms part of a binding site for TACC3 family proteins. This interaction is required for the assembly of kinetochore bridges in a trimeric complex with clathrin. Here we present the first NMR assignment of a sixth TOG domain from mini spindles as a first step to elucidate its structure and function.

show abstract

The Centrosomal Adaptor TACC3 and the Microtubule Polymerase chTOG Interact via Defined C-terminal Subdomains in an Aurora-A Kinase-independent Manner

Cited by 41 publications

References 82 publications

Xenopus TACC1 is a microtubule plus‐end tracking protein that can regulate microtubule dynamics during embryonic development

Xenopus TACC1 is a microtubule plus‐end tracking protein that can regulate microtubule dynamics during embryonic development

Oncogenic Gene Fusion FGFR3-TACC3 Is Regulated by Tyrosine Phosphorylation

Solution NMR assignment of the cryptic sixth TOG domain of mini spindles

Contact Info

Product

Resources

About