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Inactivation of the CYLD Deubiquitinase by HPV E6 Mediates Hypoxia-Induced NF-kappa B Activation

An, Jiabin; Mo, Deqiong; Liu, Huiren; Veena, Mysore S.; Srivatsan, Eri S.; Massoumi, Ramin LU and Rettig, Matthew B. (2008) In Cancer Cell 14(5). p.394-407
Abstract
The biochemical mechanisms that underlie hypoxia-induced NF-kappa B activity have remained largely undefined. Here, we find that prolonged hypoxia-induced NF-kappa B activation is restricted to cancer cell lines infected with high-risk human papillomavirus (HPV) serotypes. The HPV-encoded E6 protein is necessary and sufficient for prolonged hypoxia-induced NF-kappa B activation in these systems. The molecular target of E6 in the NF-kappa B pathway is the CYLD lysine 63 (K63) deubiquitinase, a negative regulator of the NF-kappa B pathway. Specifically, hypoxia stimulates E6-mediated ubiquitination and proteasomal degradation of CYLD. Given the established role of NF-kappa B in human carcinogenesis, these findings provide a potential... (More)
The biochemical mechanisms that underlie hypoxia-induced NF-kappa B activity have remained largely undefined. Here, we find that prolonged hypoxia-induced NF-kappa B activation is restricted to cancer cell lines infected with high-risk human papillomavirus (HPV) serotypes. The HPV-encoded E6 protein is necessary and sufficient for prolonged hypoxia-induced NF-kappa B activation in these systems. The molecular target of E6 in the NF-kappa B pathway is the CYLD lysine 63 (K63) deubiquitinase, a negative regulator of the NF-kappa B pathway. Specifically, hypoxia stimulates E6-mediated ubiquitination and proteasomal degradation of CYLD. Given the established role of NF-kappa B in human carcinogenesis, these findings provide a potential molecular/viral link between hypoxia and the adverse clinical outcomes observed in HPV-associated malignancies. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Cancer Cell
volume
14
issue
5
pages
394 - 407
publisher
Cell Press
external identifiers
  • wos:000260702800008
  • scopus:54549103311
ISSN
1878-3686
DOI
10.1016/j.ccr.2008.10.007
language
English
LU publication?
yes
id
4f1d076b-c4bf-4fad-bbfe-8739dff3416e (old id 1283969)
date added to LUP
2009-02-09 10:40:56
date last changed
2017-10-22 03:33:38
@article{4f1d076b-c4bf-4fad-bbfe-8739dff3416e,
  abstract     = {The biochemical mechanisms that underlie hypoxia-induced NF-kappa B activity have remained largely undefined. Here, we find that prolonged hypoxia-induced NF-kappa B activation is restricted to cancer cell lines infected with high-risk human papillomavirus (HPV) serotypes. The HPV-encoded E6 protein is necessary and sufficient for prolonged hypoxia-induced NF-kappa B activation in these systems. The molecular target of E6 in the NF-kappa B pathway is the CYLD lysine 63 (K63) deubiquitinase, a negative regulator of the NF-kappa B pathway. Specifically, hypoxia stimulates E6-mediated ubiquitination and proteasomal degradation of CYLD. Given the established role of NF-kappa B in human carcinogenesis, these findings provide a potential molecular/viral link between hypoxia and the adverse clinical outcomes observed in HPV-associated malignancies.},
  author       = {An, Jiabin and Mo, Deqiong and Liu, Huiren and Veena, Mysore S. and Srivatsan, Eri S. and Massoumi, Ramin and Rettig, Matthew B.},
  issn         = {1878-3686},
  language     = {eng},
  number       = {5},
  pages        = {394--407},
  publisher    = {Cell Press},
  series       = {Cancer Cell},
  title        = {Inactivation of the CYLD Deubiquitinase by HPV E6 Mediates Hypoxia-Induced NF-kappa B Activation},
  url          = {http://dx.doi.org/10.1016/j.ccr.2008.10.007},
  volume       = {14},
  year         = {2008},
}