CYLD negatively regulates cell-cycle progression by inactivating HDAC6 and increasing the levels of acetylated tubulin
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1547880
- author
- Wickstroem, Sara A. ; Masoumi, Katarzyna C. ; Khochbin, Saadi ; Faessler, Reinhard and Massoumi, Ramin LU
- organization
- publishing date
- 2010
- 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
- pmid:19893491
- 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
- 2016-04-01 13:28:13
- date last changed
- 2022-05-15 05:18:30
@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}},
keywords = {{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}},
doi = {{10.1038/emboj.2009.317}},
volume = {{29}},
year = {{2010}},
}