Tubulin tyrosine ligase like 12, a TTLL family member with SET- and TTL-like domains and roles in histone and tubulin modifications and mitosis

PLoS One. 2012;7(12):e51258. doi: 10.1371/journal.pone.0051258. Epub 2012 Dec 12.

Abstract

hTTLL12 is a member of the tubulin tyrosine ligase (TTL) family that is highly conserved in phylogeny. It has both SET-like and TTL-like domains, suggesting that it could have histone methylation and tubulin tyrosine ligase activities. Altered expression of hTTLL12 in human cells leads to specific changes in H4K20 trimethylation, and tubulin detyrosination, hTTLL12 does not catalyse histone methylation or tubulin tyrosination in vitro, as might be expected from the lack of critical amino acids in its SET-like and TTLL-like domains. hTTLL12 misexpression increases mitotic duration and chromosome numbers. These results suggest that hTTLL12 has non-catalytic functions related to tubulin and histone modification, which could be linked to its effects on mitosis and chromosome number stability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Cell Line
  • Electrophoresis, Polyacrylamide Gel
  • Histones / metabolism*
  • Humans
  • Immunoprecipitation
  • Methylation
  • Mitosis / physiology*
  • Peptide Synthases / chemistry
  • Peptide Synthases / metabolism
  • Peptide Synthases / physiology*
  • Phylogeny
  • Tubulin / metabolism*

Substances

  • Histones
  • Tubulin
  • Peptide Synthases
  • TTLL12 protein, human

Grant support

The authors are thankful for the financial support from the European Union (FP5 Procure project QLK6-2000-00159 and FP6 Prima project #504587), the Ligue Nationale Française contre le Cancer, the Ligues Départementales de Lutte contre le Cancer (Haut- and Bas-Rhin), the Association pour la Recherche sur le Cancer, the Centre National de la Recherche Scientifique, and the Institut National de la Santé et de la Recherche Médicale, the Cancéropôle Grand-Est (Axe IV and DKFZ-CGE projects) and INCa (PL099). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.