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

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

• Författare: Sara A. Wickstroem; Katarzyna C. Masoumi; Saadi Khochbin; Reinhard Faessler; Ramin Massoumi
• Avdelning/ar: Cellpatologi, Malmö; BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
• Publiceringsår: 2010
• Språk: Engelska
• Sidor: 131-144
• Publikation/Tidskrift/Serie: EMBO Journal
• Volym: 29
• Issue: 1
• Länkar: http://dx.doi.org/10.1038/emboj.2009.317
• Dokumenttyp: Artikel i tidskrift
• Förlag: Oxford University Press
• Ämne: Biochemistry and Molecular Biology
• Nyckelord: CYLD; HDAC6; cell cycle; alpha-tubulin; acetylation
• Status: Published
• Forskningsgrupp: Cell Pathology, Malmö
• ISBN/ISSN/Övrigt: ISSN: 1460-2075