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Carcinogenesis and translational controls: TACC1 is down-regulated in human cancers and associates with mRNA regulators

Oncogene volume 21, pages 5619–5630 (2002)Cite this article

Abstract

The three human TACC genes encode a family of proteins that are suspected to play a role in carcinogenesis. Their function is not precisely known; a Xenopus TACC protein called Maskin is involved in translational control, while the Drosophila D-TACC associates with microtubules and centrosomes. We have characterized the human TACC1 gene and its products. The TACC1 gene is located in region p12 of chromosome 8; its mRNA is ubiquitously expressed and encodes a protein with an apparent molecular mass of 125 kDa, which is cytoplasmic and mainly perinuclear. We show that TACC1 mRNA gene expression is down-regulated in various types of tumors. Using immunohistochemistry of tumor tissue-microarrays and sections, we confirm that the level of TACC1 protein is down-regulated in breast cancer. Finally, using the two-hybrid screen in yeast, GST pull-downs and co-immunoprecipitations, we identified two potential binding partners for TACC1, LSM7 and SmG. They constitute a conserved subfamily of Sm-like small proteins that associate with U6 snRNPs and play a role in several aspects of mRNA processing. We speculate that down-regulation of TACC1 may alter the control of mRNA homeostasis in polarized cells and participates in the oncogenic processes.

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Acknowledgements

We thank F Birg, C Mawas and D Maraninchi for discussions and support. We are especially grateful to J-P Borg and B Puig for discussions and help. This work was supported by INSERM, Institut Paoli-Calmettes, and grants from the Association pour la Recherche contre le Cancer and the Ligue Nationale contre le Cancer (Label). N Conte and B Delaval are recipients of a fellowship from MESR.

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Authors and Affiliations

  1. Département d'Oncologie Moléculaire, U119 Inserm, 27 Bd. Leï Roure, Marseille, 13009, France

    Nathalie Conte, Bénédicte Delaval & Daniel Birnbaum

  2. Département d'Oncologie Moléculaire, Laboratoire de Pathologie Moléculaire, Institut Paoli-Calmettes, Marseille, France

    Emmanuelle Charafe-Jauffret, Christophe Ginestier, Jeannine Geneix, Jocelyne Jacquemier & Daniel Birnbaum

  3. Département d'Oncologie Moléculaire, Laboratoire de Biologie des Tumeurs, Institut Paoli-Calmettes, Marseille, France

    José Adélaïde & Daniel Birnbaum

  4. Atelier de Bio-Imagerie, Institut Paoli-Calmettes, Marseille, France

    Daniel Isnardon

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  1. Nathalie Conte
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Correspondence to Daniel Birnbaum.

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Conte, N., Charafe-Jauffret, E., Delaval, B. et al. Carcinogenesis and translational controls: TACC1 is down-regulated in human cancers and associates with mRNA regulators. Oncogene 21, 5619–5630 (2002). https://doi.org/10.1038/sj.onc.1205658

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