CYLD negatively regulates cell-cycle progression by inactivating HDAC6 and increasing the levels of acetylated tubulin

• Sara A Wickström ^[1] ; Katarzyna C Masoumi ^[3] ; Saadi Khochbin ^[2] ; Reinhard Fässler ^[1] ; Ramin Massoumi ^[1]
  1. [1] Max Planck Institute of Biochemistry

     Max Planck Institute of Biochemistry

     Kreisfreie Stadt München, Alemania

     
  2. [2] Joseph Fourier University

     Joseph Fourier University

     Arrondissement de Grenoble, Francia

     
  3. [3] Department of Laboratory Medicine, Lund University, Malmö University Hospital, Malmö, Sweden

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• Localización: EMBO journal: European Molecular Biology Organization, ISSN 0261-4189, Vol. 29, Nº. 1, 2009, págs. 131-144
• Idioma: inglés
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• Resumen

  • CYLD is a tumour-suppressor gene that is mutated in a benign skin tumour syndrome called cylindromatosis. The CYLD gene product is a deubiquitinating enzyme that was shown to regulate cell proliferation, cell survival and inflammatory responses, mainly through inhibiting NF-κB signalling. Here we show that CYLD controls cell growth and division at the G1/S-phase as well as cytokinesis by associating with α-tubulin and microtubules through its CAP-Gly domains. Translocation of activated CYLD to the perinuclear region of the cell is achieved by an inhibitory interaction of CYLD with histone deacetylase-6 (HDAC6) leading to an increase in the levels of acetylated α-tubulin around the nucleus. This facilitates the interaction of CYLD with Bcl-3, leading to a significant delay in the G1-to-S-phase transition. Finally, CYLD also interacts with HDAC6 in the midbody where it regulates the rate of cytokinesis in a deubiquitinase-independent manner. Altogether these results identify a mechanism by which CYLD regulates cell proliferation at distinct cell-cycle phases.