Tubulin glycylases are required for primary cilia, control of cell proliferation and tumor development in colon.
EMBO J
; 33(19): 2247-60, 2014 Oct 01.
Article
em En
| MEDLINE
| ID: mdl-25180231
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peptídeo Sintases
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Tubulina (Proteína)
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Cílios
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Colo
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Neoplasias do Colo
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Proliferação de Células
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Glicina
Limite:
Animals
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Humans
Idioma:
En
Revista:
EMBO J
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
França