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Tubulin glycylases are required for primary cilia, control of cell proliferation and tumor development in colon
Author(s) -
Rocha Cecilia,
Papon Laura,
Cacheux Wulfran,
Marques Sousa Patricia,
Lascano Valeria,
Tort Olivia,
Giordano Tiziana,
Vacher Sophie,
Lemmers Benedicte,
Mariani Pascale,
Meseure Didier,
Medema Jan Paul,
Bièche Ivan,
Hahne Michael,
Janke Carsten
Publication year - 2014
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201488466
Subject(s) - biology , cilium , microbiology and biotechnology , cell growth , carcinogenesis , colorectal cancer , epithelium , tubulin , microtubule , cell division , cell , cancer research , cancer , genetics
TTLL 3 and TTLL 8 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 TTLL 3 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 TTLL 3‐knockout mice. Strikingly, higher proliferation is compensated by faster tissue turnover in normal colon. In a mouse model for tumorigenesis, lack of TTLL 3 strongly promotes tumor development. We further demonstrate that decreased levels of TTLL 3 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.