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Serum Response Factor Controls CYLD Expression via MAPK Signaling Pathway.

Liang, Gang ; Ahlqvist, Kristofer LU ; Pannem, Rajeswararao ; Posern, Guido and Massoumi, Ramin LU (2011) In PLoS ONE 6(5).
Abstract
Tumor suppressor gene CYLD is a deubiquitinating enzyme which negatively regulates various signaling pathways by removing the lysine 63-linked polyubiquitin chains from several specific substrates. Loss of CYLD in different types of tumors leads to either cell survival or proliferation. In this study we demonstrate that lack of CYLD expression in CYLD-/- MEFs increases proliferation rate of these cells compared to CYLD+/+ in a serum concentration dependent manner without affecting cell survival. The reduced proliferation rate in CYLD+/+ in the presence of serum was due to the binding of serum response factor (SRF) to the serum response element identified in the CYLD promoter for the up-regulation of CYLD levels. The serum regulated... (More)
Tumor suppressor gene CYLD is a deubiquitinating enzyme which negatively regulates various signaling pathways by removing the lysine 63-linked polyubiquitin chains from several specific substrates. Loss of CYLD in different types of tumors leads to either cell survival or proliferation. In this study we demonstrate that lack of CYLD expression in CYLD-/- MEFs increases proliferation rate of these cells compared to CYLD+/+ in a serum concentration dependent manner without affecting cell survival. The reduced proliferation rate in CYLD+/+ in the presence of serum was due to the binding of serum response factor (SRF) to the serum response element identified in the CYLD promoter for the up-regulation of CYLD levels. The serum regulated recruitment of SRF to the CYLD promoter was dependent on p38 mitogen-activated protein kinase (MAPK) activity. Elimination of SRF by siRNA or inhibition of p38 MAPK reduced the expression level of CYLD and increased cell proliferation. These results show that SRF acts as a positive regulator of CYLD expression, which in turn reduces the mitogenic activation of serum for aberrant proliferation of MEF cells. (Less)
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author
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publishing date
type
Contribution to journal
publication status
published
subject
in
PLoS ONE
volume
6
issue
5
article number
e19613
publisher
Public Library of Science
external identifiers
  • wos:000290256400035
  • pmid:21573132
  • scopus:79955832514
  • pmid:21573132
ISSN
1932-6203
DOI
10.1371/journal.pone.0019613
language
English
LU publication?
yes
id
fe26c139-be5e-4160-bab5-c0440dc6ea5b (old id 1972571)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21573132?dopt=Abstract
date added to LUP
2016-04-04 09:20:18
date last changed
2021-07-06 02:56:56
@article{fe26c139-be5e-4160-bab5-c0440dc6ea5b,
  abstract     = {Tumor suppressor gene CYLD is a deubiquitinating enzyme which negatively regulates various signaling pathways by removing the lysine 63-linked polyubiquitin chains from several specific substrates. Loss of CYLD in different types of tumors leads to either cell survival or proliferation. In this study we demonstrate that lack of CYLD expression in CYLD-/- MEFs increases proliferation rate of these cells compared to CYLD+/+ in a serum concentration dependent manner without affecting cell survival. The reduced proliferation rate in CYLD+/+ in the presence of serum was due to the binding of serum response factor (SRF) to the serum response element identified in the CYLD promoter for the up-regulation of CYLD levels. The serum regulated recruitment of SRF to the CYLD promoter was dependent on p38 mitogen-activated protein kinase (MAPK) activity. Elimination of SRF by siRNA or inhibition of p38 MAPK reduced the expression level of CYLD and increased cell proliferation. These results show that SRF acts as a positive regulator of CYLD expression, which in turn reduces the mitogenic activation of serum for aberrant proliferation of MEF cells.},
  author       = {Liang, Gang and Ahlqvist, Kristofer and Pannem, Rajeswararao and Posern, Guido and Massoumi, Ramin},
  issn         = {1932-6203},
  language     = {eng},
  number       = {5},
  publisher    = {Public Library of Science},
  series       = {PLoS ONE},
  title        = {Serum Response Factor Controls CYLD Expression via MAPK Signaling Pathway.},
  url          = {https://lup.lub.lu.se/search/files/5297373/1975833.pdf},
  doi          = {10.1371/journal.pone.0019613},
  volume       = {6},
  year         = {2011},
}