Dissemin is shutting down on January 1st, 2025

Published in

EMBO Press, The EMBO Journal, 22(33), p. 2735-2735, 2014

DOI: 10.15252/embj.201490279

EMBO Press, The EMBO Journal, 19(33), p. 2247-2260, 2014

DOI: 10.15252/embj.201488466

Links

Tools

Export citation

Search in Google Scholar

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

Journal article published in 2014 by Cecilia Rocha, Laura Papon, Patricia Marques Sousa, Wulfran Cacheux, Olivia Tort, Patricia Marques Sousa, Valeria Lascano, Sophie Vacher, Tiziana Giordano, Benedicte Lemmers, Pascale Mariani, Jan Paul Medema, Didier Meseure ORCID, Ivan Bièche, Michael Hahne and other authors.
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

Full text: Download

Green circle
Preprint: archiving allowed
Upload
Orange circle
Postprint: archiving restricted
Upload
Red circle
Published version: archiving forbidden
Policy details
Data provided by SHERPA/RoMEO

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.