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

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

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review

114 Citeringar (SciVal)

Sammanfattning

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
Originalspråkengelska
Sidor (från-till)131-144
TidskriftEMBO Journal
Volym29
Utgåva1
DOI
StatusPublished - 2010

Ämnesklassifikation (UKÄ)

  • Biokemi och molekylärbiologi

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