2. Academic Validation
  3. Tubulin glycylases are required for primary cilia, control of cell proliferation and tumor development in colon

Tubulin glycylases are required for primary cilia, control of cell proliferation and tumor development in colon

  • EMBO J. 2014 Oct 1;33(19):2247-60. doi: 10.15252/embj.201488466.
Cecilia Rocha 1,  Laura Papon 2,  Wulfran Cacheux 3,  Patricia Marques Sousa 4,  Valeria Lascano 5,  Olivia Tort 6,  Tiziana Giordano 4,  Sophie Vacher 3,  Benedicte Lemmers 2,  Pascale Mariani 3,  Didier Meseure 3,  Jan Paul Medema 5,  Ivan Bièche 3,  Michael Hahne 7,  Carsten Janke 8
Affiliations

Affiliations

  • 1 Institut Curie, Orsay, France PSL Research University, Paris, France CNRS UMR3306, Orsay, France INSERM U1005, Orsay, France IGMM CNRS UMR5535, Montpellier, France Université Montpellier Sud de France, Montpellier, France.
  • 2 IGMM CNRS UMR5535, Montpellier, France Université Montpellier Sud de France, Montpellier, France.
  • 3 Institut Curie Hospital, Paris, France.
  • 4 Institut Curie, Orsay, France PSL Research University, Paris, France CNRS UMR3306, Orsay, France INSERM U1005, Orsay, France.
  • 5 Academic Medical Center, Amsterdam, The Netherlands.
  • 6 Institut Curie, Orsay, France PSL Research University, Paris, France CNRS UMR3306, Orsay, France INSERM U1005, Orsay, France Institut de Biotecnologia i de Biomedicina, Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, Bellaterra (Barcelona), Spain.
  • 7 IGMM CNRS UMR5535, Montpellier, France Université Montpellier Sud de France, Montpellier, France Academic Medical Center, Amsterdam, The Netherlands carsten.janke@curie.fr hahne@igmm.cnrs.fr.
  • 8 Institut Curie, Orsay, France PSL Research University, Paris, France CNRS UMR3306, Orsay, France INSERM U1005, Orsay, France carsten.janke@curie.fr hahne@igmm.cnrs.fr.
PMID: 25180231 DOI: 10.15252/embj.201488466
Abstract

TTLL3 and TTLL8 are tubulin glycine ligases catalyzing posttranslational glycylation of microtubules. We show here for the first time that these Enzymes are required for robust formation of primary cilia. We further discover the existence of primary cilia in colon and demonstrate that TTLL3 is the only glycylase in this organ. As a consequence, colon epithelium shows a reduced number of primary cilia accompanied by an increased rate of cell division in TTLL3-knockout mice. Strikingly, higher proliferation is compensated by faster tissue turnover in normal colon. In a mouse model for tumorigenesis, lack of TTLL3 strongly promotes tumor development. We further demonstrate that decreased levels of TTLL3 expression are linked to the development of human colorectal carcinomas. Thus, we have uncovered a novel role for tubulin glycylation in primary cilia maintenance, which controls cell proliferation of colon epithelial cells and plays an essential role in colon Cancer development.

Keywords

colorectal cancer; microtubule glycylation; primary cilia; proliferation; tubulin posttranslational modification.

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