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Deubiquitinating activity of CYLD is impaired by SUMOylation in neuroblastoma cells.

Kobayashi, Tamae LU ; Masoumi, Katarzyna LU and Massoumi, Ramin LU (2015) In Oncogene 34(17). p.2251-2260
Abstract
CYLD is a deubiquitinating (DUB) enzyme that has a pivotal role in modulating nuclear factor kappa B (NF-κB) signaling pathways by removing the lysine 63- and linear-linked ubiquitin chain from substrates such as tumor necrosis factor receptor-associated factor 2 (TRAF2) and TRAF6. Loss of CYLD activity is associated with tumorigenicity, and levels of CYLD are lost or downregulated in different types of human tumors. In the present study, we found that high CYLD expression was associated with better overall survival and relapse-free neuroblastoma patient outcome, as well as inversely correlated with the stage of neuroblastoma. Retinoic acid-mediated differentiation of neuroblastoma restored CYLD expression and promoted SUMOylation of CYLD.... (More)
CYLD is a deubiquitinating (DUB) enzyme that has a pivotal role in modulating nuclear factor kappa B (NF-κB) signaling pathways by removing the lysine 63- and linear-linked ubiquitin chain from substrates such as tumor necrosis factor receptor-associated factor 2 (TRAF2) and TRAF6. Loss of CYLD activity is associated with tumorigenicity, and levels of CYLD are lost or downregulated in different types of human tumors. In the present study, we found that high CYLD expression was associated with better overall survival and relapse-free neuroblastoma patient outcome, as well as inversely correlated with the stage of neuroblastoma. Retinoic acid-mediated differentiation of neuroblastoma restored CYLD expression and promoted SUMOylation of CYLD. This posttranslational modification inhibited deubiquitinase activity of CYLD against TRAF2 and TRAF6 and facilitated NF-κB signaling. Overexpression of non-SUMOylatable mutant CYLD in neuroblastoma cells reduced retinoic acid-induced NF-κB activation and differentiation of cells, but instead promoted cell death.Oncogene advance online publication, 9 June 2014; doi:10.1038/onc.2014.159. (Less)
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Contribution to journal
publication status
published
subject
in
Oncogene
volume
34
issue
17
pages
2251 - 2260
publisher
Nature Publishing Group
external identifiers
  • pmid:24909169
  • wos:000353473000010
  • scopus:84933525942
ISSN
1476-5594
DOI
10.1038/onc.2014.159
language
English
LU publication?
yes
id
f49a50d3-7aa6-465c-b6e4-a22d2ba755be (old id 4529032)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/24909169?dopt=Abstract
date added to LUP
2014-07-04 17:29:52
date last changed
2017-07-23 03:08:38
@article{f49a50d3-7aa6-465c-b6e4-a22d2ba755be,
  abstract     = {CYLD is a deubiquitinating (DUB) enzyme that has a pivotal role in modulating nuclear factor kappa B (NF-κB) signaling pathways by removing the lysine 63- and linear-linked ubiquitin chain from substrates such as tumor necrosis factor receptor-associated factor 2 (TRAF2) and TRAF6. Loss of CYLD activity is associated with tumorigenicity, and levels of CYLD are lost or downregulated in different types of human tumors. In the present study, we found that high CYLD expression was associated with better overall survival and relapse-free neuroblastoma patient outcome, as well as inversely correlated with the stage of neuroblastoma. Retinoic acid-mediated differentiation of neuroblastoma restored CYLD expression and promoted SUMOylation of CYLD. This posttranslational modification inhibited deubiquitinase activity of CYLD against TRAF2 and TRAF6 and facilitated NF-κB signaling. Overexpression of non-SUMOylatable mutant CYLD in neuroblastoma cells reduced retinoic acid-induced NF-κB activation and differentiation of cells, but instead promoted cell death.Oncogene advance online publication, 9 June 2014; doi:10.1038/onc.2014.159.},
  author       = {Kobayashi, Tamae and Masoumi, Katarzyna and Massoumi, Ramin},
  issn         = {1476-5594},
  language     = {eng},
  number       = {17},
  pages        = {2251--2260},
  publisher    = {Nature Publishing Group},
  series       = {Oncogene},
  title        = {Deubiquitinating activity of CYLD is impaired by SUMOylation in neuroblastoma cells.},
  url          = {http://dx.doi.org/10.1038/onc.2014.159},
  volume       = {34},
  year         = {2015},
}