Cyld inhibits tumor cell proliferation by blocking Bcl-3-dependent NF-kappaB signaling
(2006) In Cell 125(4). p.665-677- Abstract
- Mutations in the CYLD gene cause tumors of hair-follicle keratinocytes. The CYLD gene encodes a deubiquitinase that removes lysine 63-linked ubiquitin chains from TRAF2 and inhibits p65/p50 NF-kappaB activation. Here we show that mice lacking Cyld are highly susceptible to chemically induced skin tumors. Cyld-/- tumors and keratinocytes treated with 12-O-tetradecanoylphorbol-13 acetate (TPA) or UV light are hyperproliferative and have elevated cyclin D1 levels. The cyclin D1 elevation is caused not by increased p65/p50 action but rather by increased nuclear activity of Bcl-3-associated NF-kappaB p50 and p52. In Cyld+/+ keratinocytes, TPA or UV light triggers the translocation of Cyld from the cytoplasm to the perinuclear region, where Cyld... (More)
- Mutations in the CYLD gene cause tumors of hair-follicle keratinocytes. The CYLD gene encodes a deubiquitinase that removes lysine 63-linked ubiquitin chains from TRAF2 and inhibits p65/p50 NF-kappaB activation. Here we show that mice lacking Cyld are highly susceptible to chemically induced skin tumors. Cyld-/- tumors and keratinocytes treated with 12-O-tetradecanoylphorbol-13 acetate (TPA) or UV light are hyperproliferative and have elevated cyclin D1 levels. The cyclin D1 elevation is caused not by increased p65/p50 action but rather by increased nuclear activity of Bcl-3-associated NF-kappaB p50 and p52. In Cyld+/+ keratinocytes, TPA or UV light triggers the translocation of Cyld from the cytoplasm to the perinuclear region, where Cyld binds and deubiquitinates Bcl-3, thereby preventing nuclear accumulation of Bcl-3 and p50/Bcl-3- or p52/Bcl-3-dependent proliferation. These data indicate that, depending on the external signals, Cyld can negatively regulate different NF-kappaB pathways; inactivation of TRAF2 controls survival and inflammation, while inhibition of Bcl-3 controls proliferation and tumor growth. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1136403
- author
- Massoumi, Ramin LU ; Chmielarska, Katarzyna ; Hennecke, Katharina ; Pfeifer, Alexander and Fassler, Reinhard
- organization
- publishing date
- 2006
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Cell
- volume
- 125
- issue
- 4
- pages
- 665 - 677
- publisher
- Cell Press
- external identifiers
-
- pmid:16713561
- scopus:33646531810
- ISSN
- 1097-4172
- DOI
- 10.1016/j.cell.2006.03.041
- language
- English
- LU publication?
- yes
- id
- 07a4ce8e-e1d4-48c8-886c-23b9a0b66216 (old id 1136403)
- date added to LUP
- 2016-04-01 12:08:17
- date last changed
- 2022-05-14 18:06:08
@article{07a4ce8e-e1d4-48c8-886c-23b9a0b66216,
abstract = {{Mutations in the CYLD gene cause tumors of hair-follicle keratinocytes. The CYLD gene encodes a deubiquitinase that removes lysine 63-linked ubiquitin chains from TRAF2 and inhibits p65/p50 NF-kappaB activation. Here we show that mice lacking Cyld are highly susceptible to chemically induced skin tumors. Cyld-/- tumors and keratinocytes treated with 12-O-tetradecanoylphorbol-13 acetate (TPA) or UV light are hyperproliferative and have elevated cyclin D1 levels. The cyclin D1 elevation is caused not by increased p65/p50 action but rather by increased nuclear activity of Bcl-3-associated NF-kappaB p50 and p52. In Cyld+/+ keratinocytes, TPA or UV light triggers the translocation of Cyld from the cytoplasm to the perinuclear region, where Cyld binds and deubiquitinates Bcl-3, thereby preventing nuclear accumulation of Bcl-3 and p50/Bcl-3- or p52/Bcl-3-dependent proliferation. These data indicate that, depending on the external signals, Cyld can negatively regulate different NF-kappaB pathways; inactivation of TRAF2 controls survival and inflammation, while inhibition of Bcl-3 controls proliferation and tumor growth.}},
author = {{Massoumi, Ramin and Chmielarska, Katarzyna and Hennecke, Katharina and Pfeifer, Alexander and Fassler, Reinhard}},
issn = {{1097-4172}},
language = {{eng}},
number = {{4}},
pages = {{665--677}},
publisher = {{Cell Press}},
series = {{Cell}},
title = {{Cyld inhibits tumor cell proliferation by blocking Bcl-3-dependent NF-kappaB signaling}},
url = {{http://dx.doi.org/10.1016/j.cell.2006.03.041}},
doi = {{10.1016/j.cell.2006.03.041}},
volume = {{125}},
year = {{2006}},
}