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

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Author

  • Sara A. Wickstroem
  • Katarzyna C. Masoumi
  • Saadi Khochbin
  • Reinhard Faessler
  • Ramin Massoumi

Summary, in English

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-kappa B signalling. Here we show that CYLD controls cell growth and division at the G(1)/S-phase as well as cytokinesis by associating with alpha-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 alpha-tubulin around the nucleus. This facilitates the interaction of CYLD with Bcl-3, leading to a significant delay in the G(1)-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. The EMBO Journal (2010) 29, 131-144. doi: 10.1038/emboj.2009.317; Published online 5 November 2009

Department/s

  • Cell Pathology, Malmö
  • BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation

Publishing year

2010

Language

English

Pages

131-144

Publication/Series

EMBO Journal

Volume

29

Issue

1

Document type

Journal article

Publisher

Oxford University Press

Topic

  • Biochemistry and Molecular Biology

Keywords

  • CYLD
  • HDAC6
  • cell cycle
  • alpha-tubulin
  • acetylation

Status

Published

Research group

  • Cell Pathology, Malmö

ISBN/ISSN/Other

  • ISSN: 1460-2075