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

Wickstroem, Sara A.; Masoumi, Katarzyna C.; Khochbin, Saadi; Faessler, Reinhard and Massoumi, Ramin LU (2010) In EMBO Journal 29(1). p.131-144
Abstract
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... (More)
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 (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
CYLD, HDAC6, cell cycle, alpha-tubulin, acetylation
in
EMBO Journal
volume
29
issue
1
pages
131 - 144
publisher
Oxford University Press
external identifiers
  • wos:000273358100013
  • scopus:75649119696
ISSN
1460-2075
DOI
10.1038/emboj.2009.317
language
English
LU publication?
yes
id
7a205a00-68dc-4909-ad13-58d1793159a7 (old id 1547880)
date added to LUP
2010-02-23 08:47:08
date last changed
2018-07-15 03:46:32
@article{7a205a00-68dc-4909-ad13-58d1793159a7,
  abstract     = {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},
  author       = {Wickstroem, Sara A. and Masoumi, Katarzyna C. and Khochbin, Saadi and Faessler, Reinhard and Massoumi, Ramin},
  issn         = {1460-2075},
  keyword      = {CYLD,HDAC6,cell cycle,alpha-tubulin,acetylation},
  language     = {eng},
  number       = {1},
  pages        = {131--144},
  publisher    = {Oxford University Press},
  series       = {EMBO Journal},
  title        = {CYLD negatively regulates cell-cycle progression by inactivating HDAC6 and increasing the levels of acetylated tubulin},
  url          = {http://dx.doi.org/10.1038/emboj.2009.317},
  volume       = {29},
  year         = {2010},
}