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Transforming acidic coiled-coil (TACC) proteins

Congran Zhao, Xiaofeng He, Heng Li, Jihui Zhou, Xiuying Han, Dongjun Wang, Guofeng Tian, Fuge Sui
TACC3, a member of the transforming acidic coiled-coil protein (TACC) family, is a multifunctional protein that is involved in various biological functions, including proliferation and differentiation of tumor cells, cancer progression and metastasis. The aims of the present study were to examine whether TACC3 expression is associated with the proliferation and migration of osteosarcoma (OS) cells and to investigate the potential underlying molecular mechanisms of TACC3 in OS. First, the levels of mRNA and protein expression in OS cell lines by reverse transcription-quantitative polymerase chain reaction and western blotting, respectively were examined...
May 2018: Oncology Letters
Sourav Sarkar, Ellis L Ryan, Stephen J Royle
Fibroblast growth factor receptor 3-transforming acidic coiled-coil containing protein 3 (FGFR3-TACC3; FT3) is a gene fusion resulting from rearrangement of chromosome 4 that has been identified in many cancers including those of the urinary bladder. Altered FGFR3 signalling in FT3-positive cells is thought to contribute to cancer progression. However, potential changes in TACC3 function in these cells have not been explored. TACC3 is a mitotic spindle protein required for accurate chromosome segregation. Errors in segregation lead to aneuploidy, which can contribute to cancer progression...
August 2017: Open Biology
Feng Guo, Yaquan Liu
Transforming acidic coiled-coil protein 3 (TACC3) is a member of the TACC family and plays an important role in regulating cell mitosis, transcription, and tumorigenesis. However, the expression pattern and roles of TACC3 in renal cell carcinoma (RCC) remain unclear. The aim of this study was to investigate the role of TACC3 in RCC. We demonstrated overexpression of TACC3 in human RCC cell lines at both RNA and protein levels. Moreover, knockdown of TACC3 repressed RCC cell proliferation, migration, and invasion in vitro...
March 5, 2018: Oncology Research
Xiaojun Zhu, Qianqian Cao, Xia Li, Zhengping Wang
The insufficient invasion of trophoblasts is known to be correlated with the development of preeclampsia. Transforming acidic coiled‑coil protein 3 (TACC3), a member of the TACC domain family, is important in the regulation of cell differentiation, migration and invasion. However, the role of TACC3 in trophoblast function during placental development remains to be fully elucidated. The present study aimed to determine the expression and function of TACC3 in human placenta and to examine the underlying mechanisms...
October 2016: Molecular Medicine Reports
Erin L Rutherford, Leslie Carandang, Patrick T Ebbert, Alexandra N Mills, Jackson T Bowers, Laura Anne Lowery
Microtubule dynamics is regulated by plus end-tracking proteins (+TIPs), which localize to the plus ends of microtubules (MTs). We previously showed that TACC1 and TACC3, members of the transforming acidic coiled-coil protein family, can act as +TIPs to regulate MT dynamics in Xenopus laevis Here we characterize TACC2 as a +TIP that localizes to MT plus ends in front of EB1 and overlapping with TACC1 and TACC3 in multiple embryonic cell types. We also show that TACC2 can promote MT polymerization in mesenchymal cells but not neuronal growth cones, thus displaying cell-type specificity...
October 15, 2016: Molecular Biology of the Cell
Yoshiaki Onodera, Kiyoshi Takagi, Yasuhiro Miki, Ken-Ichi Takayama, Yukiko Shibahara, Mika Watanabe, Takanori Ishida, Satoshi Inoue, Hironobu Sasano, Takashi Suzuki
Transforming acidic coiled-coil protein 2 (TACC2) belongs to TACC family proteins and involved in a variety of cellular processes through interactions with some molecules involved in centrosomes/microtubules dynamics. Mounting evidence suggests that TACCs is implicated in the progression of some human malignancies, but significance of TACC2 protein in breast carcinoma is still unknown. Therefore, in this study, we examined the clinical significance of TACC2 in breast carcinoma and biological functions by immunohistochemistry and in vitro experiments...
August 2016: Cancer Medicine
Katelyn N Nelson, April N Meyer, Asma Siari, Alexandre R Campos, Khatereh Motamedchaboki, Daniel J Donoghue
UNLABELLED: 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...
May 2016: Molecular Cancer Research: MCR
Feng Jiang, Bohua Kuang, Yi Que, Zhirui Lin, Li Yuan, Wei Xiao, Ruiqing Peng, Xiaoshi Zhang, Xing Zhang
The relationship between TACC3, a member of the transforming acidic coiled-coil proteins (TACCs) family, and lung carcinoma remains unclear. The present study was designed to explore the prognostic and clinical significance of TACC3 in non-small cell lung cancer (NSCLC). An immunohistochemistry (IHC) assay was performed to analyze the expression of TACC3 in 195 lung cancer cases. The mRNA and protein levels of TACC3 were examined by quantitative reverse transcription-PCR or western blotting. The correlation between TACC3 expression and clinicopathological factors was analyzed by χ2 analysis and Fisher's exact test...
January 2016: Oncology Reports
Lizhen Chen, Marian Chuang, Thijs Koorman, Mike Boxem, Yishi Jin, Andrew D Chisholm
Axon injury triggers a series of changes in the axonal cytoskeleton that are prerequisites for effective axon regeneration. In Caenorhabditis elegans the signaling protein Exchange Factor for ARF-6 (EFA-6) is a potent intrinsic inhibitor of axon regrowth. Here we show that axon injury triggers rapid EFA-6-dependent inhibition of axonal microtubule (MT) dynamics, concomitant with relocalization of EFA-6. EFA-6 relocalization and axon regrowth inhibition require a conserved 18-aa motif in its otherwise intrinsically disordered N-terminal domain...
2015: ELife
Mahdi Mahdipour, Ana Rita Canhoto Leitoguinho, Ricardo A Zacarias Silva, Helena T A van Tol, Tom A E Stout, Gabriela Rodrigues, Bernard A J Roelen
Transforming acidic coiled-coil (TACC) proteins are key players during mitosis via stabilization of the spindle. The roles of TACCs during meiosis are however less clear. We used bovine oocytes to study the expression and function of TACC3 during meiosis. TACC3 mRNA was detected in bovine oocytes during meiosis using qRT-PCR, and while it was also expressed in cleavage stage embryos, its expression was down-regulated at the morula and blastocyst stages. Immunofluorescence was used to demonstrate that TACC3 co-localized with tubulin in the metaphase I and II spindles...
2015: PloS One
Christopher M Lucaj, Matthew F Evans, Belinda U Nwagbara, Patrick T Ebbert, Charlie C Baker, Joseph G Volk, Andrew F Francl, Sean P Ruvolo, Laura Anne Lowery
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...
May 2015: Cytoskeleton
Gulnahar B Mortuza, Tommaso Cavazza, Maria Flor Garcia-Mayoral, Dario Hermida, Isabel Peset, Juan G Pedrero, Nekane Merino, Francisco J Blanco, Jeppe Lyngsø, Marta Bruix, Jan Skov Pedersen, Isabelle Vernos, Guillermo Montoya
chTOG is a conserved microtubule polymerase that catalyses the addition of tubulin dimers to promote microtubule growth. chTOG interacts with TACC3, a member of the transforming acidic coiled-coil (TACC) family. Here we analyse their association using the Xenopus homologues, XTACC3 (TACC3) and XMAP215 (chTOG), dissecting the mechanism by which their interaction promotes microtubule elongation during spindle assembly. Using SAXS, we show that the TACC domain (TD) is an elongated structure that mediates the interaction with the C terminus of XMAP215...
2014: Nature Communications
Puja Singh, Geethu Emily Thomas, Koyikulangara K Gireesh, Tapas K Manna
Centrosome-mediated microtubule nucleation is essential for spindle assembly during mitosis. Although γ-tubulin complexes have primarily been implicated in the nucleation process, details of the underlying mechanisms remain poorly understood. Here, we demonstrated that a member of the human transforming acidic coiled-coil (TACC) protein family, TACC3, plays a critical role in microtubule nucleation at the centrosome. In mitotic cells, TACC3 knockdown substantially affected the assembly of microtubules in the astral region and impaired microtubule nucleation at the centrosomes...
November 14, 2014: Journal of Biological Chemistry
Belinda U Nwagbara, Anna E Faris, Elizabeth A Bearce, Burcu Erdogan, Patrick T Ebbert, Matthew F Evans, Erin L Rutherford, Tiffany B Enzenbacher, Laura Anne Lowery
Microtubule plus end dynamics are regulated by a conserved family of proteins called plus end-tracking proteins (+TIPs). It is unclear how various +TIPs interact with each other and with plus ends to control microtubule behavior. The centrosome-associated protein TACC3, a member of the transforming acidic coiled-coil (TACC) domain family, has been implicated in regulating several aspects of microtubule dynamics. However, TACC3 has not been shown to function as a +TIP in vertebrates. Here we show that TACC3 promotes axon outgrowth and regulates microtubule dynamics by increasing microtubule plus end velocities in vivo...
November 1, 2014: Molecular Biology of the Cell
Fan Zheng, Tianpeng Li, Dong-Yan Jin, Viktoriya Syrovatkina, Kathleen Scheffler, Phong T Tran, Chuanhai Fu
Accurate chromosome segregation requires timely bipolar spindle formation during mitosis. The transforming acidic coiled-coil (TACC) family proteins and the ch-TOG family proteins are key players in bipolar spindle formation. They form a complex to stabilize spindle microtubules, mainly dependent on their localization to the centrosome (the spindle pole body [SPB] in yeast). The molecular mechanism underlying the targeting of the TACC-ch-TOG complex to the centrosome remains unclear. Here we show that the fission yeast Schizosaccharomyces pombe TACC orthologue alp7p is recruited to the SPB by csi1p...
September 15, 2014: Molecular Biology of the Cell
Naoyuki Okada, Takashi Toda, Masayuki Yamamoto, Masamitsu Sato
As cells transition from interphase to mitosis, the microtubule cytoskeleton is reorganized to form the mitotic spindle. In the closed mitosis of fission yeast, a microtubule-associated protein complex, Alp7-Alp14 (transforming acidic coiled-coil-tumor overexpressed gene), enters the nucleus upon mitotic entry and promotes spindle formation. However, how the complex is controlled to accumulate in the nucleus only during mitosis remains elusive. Here we demonstrate that Alp7-Alp14 is excluded from the nucleus during interphase using the nuclear export signal in Alp14 but is accumulated in the nucleus during mitosis through phosphorylation of Alp7 by the cyclin-dependent kinase (CDK)...
July 1, 2014: Molecular Biology of the Cell
Harish C Thakur, Madhurendra Singh, Luitgard Nagel-Steger, Jana Kremer, Daniel Prumbaum, Eyad Kalawy Fansa, Hakima Ezzahoini, Kazem Nouri, Lothar Gremer, André Abts, Lutz Schmitt, Stefan Raunser, Mohammad R Ahmadian, Roland P Piekorz
The cancer-associated, centrosomal adaptor protein TACC3 (transforming acidic coiled-coil 3) and its direct effector, the microtubule polymerase chTOG (colonic and hepatic tumor overexpressed gene), play a crucial function in centrosome-driven mitotic spindle assembly. It is unclear how TACC3 interacts with chTOG. Here, we show that the C-terminal TACC domain of TACC3 and a C-terminal fragment adjacent to the TOG domains of chTOG mediate the interaction between these two proteins. Interestingly, the TACC domain consists of two functionally distinct subdomains, CC1 (amino acids (aa) 414-530) and CC2 (aa 530-630)...
January 3, 2014: Journal of Biological Chemistry
R Yao, Y Kondoh, Y Natsume, H Yamanaka, M Inoue, H Toki, R Takagi, T Shimizu, T Yamori, H Osada, T Noda
The mitotic spindle is assembled by the coordinated action of centrosomes and kinetochore microtubules. An evolutionally conserved protein family, transforming acidic coiled-coil (TACC), has been shown to be involved in this process. In humans, TACC3 is aberrantly expressed in a variety of human cancers, but its biological significance remains to be elucidated. Here, using a novel compound targeting TACC3, spindlactone (SPL), we show that the perturbation of TACC3 selectively inhibited the nucleation of centrosome microtubules in ovarian cancer cells...
August 14, 2014: Oncogene
Geun-Hyoung Ha, Jung-Lye Kim, Eun-Kyoung Breuer, Eun-Kyoung Yim Breuer
The third member of transforming acidic coiled-coil protein (TACC) family, TACC3, has been shown to be an important player in the regulation of centrosome/microtubule dynamics during mitosis and found to be deregulated in a variety of human malignancies. Our previous studies have suggested that TACC3 may be involved in cervical cancer progression and chemoresistance, and its overexpression can induce epithelial-mesenchymal transition (EMT) by activating the phosphatidylinositol 3-kinase (PI3K)/Akt and extracellular signal-regulated protein kinases (ERKs) signal transduction pathways...
2013: PloS One
Fiona E Hood, Samantha J Williams, Selena G Burgess, Mark W Richards, Daniel Roth, Anne Straube, Mark Pfuhl, Richard Bayliss, Stephen J Royle
A complex of transforming acidic coiled-coil protein 3 (TACC3), colonic and hepatic tumor overexpressed gene (ch-TOG), and clathrin has been implicated in mitotic spindle assembly and in the stabilization of kinetochore fibers by cross-linking microtubules. It is unclear how this complex binds microtubules and how the proteins in the complex interact with one another. TACC3 and clathrin have each been proposed to be the spindle recruitment factor. We have mapped the interactions within the complex and show that TACC3 and clathrin were interdependent for spindle recruitment, having to interact in order for either to be recruited to the spindle...
August 5, 2013: Journal of Cell Biology
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