Added by | amaraver |
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Group name | EquipeAM |
Item Type | Journal Article |
Title | Tubulin glycylases are required for primary cilia, control of cell proliferation and tumor development in colon |
Creator | Rocha et al. |
Author | Cecilia Rocha |
Author | Laura Papon |
Author | Wulfran Cacheux |
Author | Patricia Marques Sousa |
Author | Valeria Lascano |
Author | Olivia Tort |
Author | Tiziana Giordano |
Author | Sophie Vacher |
Author | Benedicte Lemmers |
Author | Pascale Mariani |
Author | Didier Meseure |
Author | Jan Paul Medema |
Author | Ivan Bièche |
Author | Michael Hahne |
Author | Carsten Janke |
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. |
Publication | The EMBO journal |
Volume | 33 |
Issue | 19 |
Pages | 2247-2260 |
Date | Oct 01, 2014 |
Journal Abbr | EMBO J. |
Language | eng |
DOI | 10.15252/embj.201488466 |
ISSN | 1460-2075 |
Library Catalog | PubMed |
Extra | PMID: 25180231 PMCID: PMC4282510 |
Tags | Animals, Blotting, Western, Carcinogens, Cell Proliferation, Cells, Cultured, Cilia, Colon, Colonic Neoplasms, colorectal cancer, Colorectal Neoplasms, Disease Models, Animal, Embryo, Mammalian, Epithelial Cells, Fibroblasts, Glycine, Humans, Immunoenzyme Techniques, Mice, Mice, Knockout, microtubule glycylation, Microtubules, original, Peptide Synthases, primary cilia, proliferation, Protein Processing, Post-Translational, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, RNA, Messenger, Tubulin, tubulin posttranslational modification |
Date Added | 2019/05/16 - 11:50:51 |
Date Modified | 2019/05/16 - 11:51:17 |
Notes and Attachments | Full Text (Attachment) PubMed entry (Attachment) |