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Human S100A9 Protein Is Stabilized by Inflammatory Stimuli via the Formation of Proteolytically-Resistant Homodimers.

Riva, Matteo LU ; He, Zhifei LU ; Källberg, Eva LU ; Ivars, Fredrik LU and Leanderson, Tomas (2013) In PLoS ONE 8(4).
Abstract
S100A8 and S100A9 are Ca(2+)-binding proteins that are associated with acute and chronic inflammation and cancer. They form predominantly heterodimers even if there are data supporting homodimer formation. We investigated the stability of the heterodimer in myeloid and S100A8/S100A9 over-expressing COS cells. In both cases, S100A8 and S100A9 proteins were not completely degraded even 48 hrs after blocking protein synthesis. In contrast, in single transfected cells, S100A8 protein was completely degraded after 24 h, while S100A9 was completely unstable. However, S100A9 protein expression was rescued upon S100A8 co-expression or inhibition of proteasomal activity. Furthermore, S100A9, but not S100A8, could be stabilized by LPS, IL-1β and... (More)
S100A8 and S100A9 are Ca(2+)-binding proteins that are associated with acute and chronic inflammation and cancer. They form predominantly heterodimers even if there are data supporting homodimer formation. We investigated the stability of the heterodimer in myeloid and S100A8/S100A9 over-expressing COS cells. In both cases, S100A8 and S100A9 proteins were not completely degraded even 48 hrs after blocking protein synthesis. In contrast, in single transfected cells, S100A8 protein was completely degraded after 24 h, while S100A9 was completely unstable. However, S100A9 protein expression was rescued upon S100A8 co-expression or inhibition of proteasomal activity. Furthermore, S100A9, but not S100A8, could be stabilized by LPS, IL-1β and TNFα treatment. Interestingly, stimulation of S100A9-transfected COS cells with proteasomal inhibitor or IL-1β lead to the formation of protease resistant S100A9 homodimers. In summary, our data indicated that S100A9 protein is extremely unstable but can be rescued upon co-expression with S100A8 protein or inflammatory stimuli, via proteolytically resistant homodimer formation. The formation of S100A9 homodimers by this mechanism may constitute an amplification step during an inflammatory reaction. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
PLoS ONE
volume
8
issue
4
article number
e61832
publisher
Public Library of Science (PLoS)
external identifiers
  • wos:000318008400100
  • pmid:23626736
  • scopus:84876571161
ISSN
1932-6203
DOI
10.1371/journal.pone.0061832
language
English
LU publication?
yes
id
0be44fad-4ba7-48e8-afc4-2ecc306e78f1 (old id 3733232)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/23626736?dopt=Abstract
date added to LUP
2016-04-01 13:16:34
date last changed
2022-01-27 18:18:44
@article{0be44fad-4ba7-48e8-afc4-2ecc306e78f1,
  abstract     = {{S100A8 and S100A9 are Ca(2+)-binding proteins that are associated with acute and chronic inflammation and cancer. They form predominantly heterodimers even if there are data supporting homodimer formation. We investigated the stability of the heterodimer in myeloid and S100A8/S100A9 over-expressing COS cells. In both cases, S100A8 and S100A9 proteins were not completely degraded even 48 hrs after blocking protein synthesis. In contrast, in single transfected cells, S100A8 protein was completely degraded after 24 h, while S100A9 was completely unstable. However, S100A9 protein expression was rescued upon S100A8 co-expression or inhibition of proteasomal activity. Furthermore, S100A9, but not S100A8, could be stabilized by LPS, IL-1β and TNFα treatment. Interestingly, stimulation of S100A9-transfected COS cells with proteasomal inhibitor or IL-1β lead to the formation of protease resistant S100A9 homodimers. In summary, our data indicated that S100A9 protein is extremely unstable but can be rescued upon co-expression with S100A8 protein or inflammatory stimuli, via proteolytically resistant homodimer formation. The formation of S100A9 homodimers by this mechanism may constitute an amplification step during an inflammatory reaction.}},
  author       = {{Riva, Matteo and He, Zhifei and Källberg, Eva and Ivars, Fredrik and Leanderson, Tomas}},
  issn         = {{1932-6203}},
  language     = {{eng}},
  number       = {{4}},
  publisher    = {{Public Library of Science (PLoS)}},
  series       = {{PLoS ONE}},
  title        = {{Human S100A9 Protein Is Stabilized by Inflammatory Stimuli via the Formation of Proteolytically-Resistant Homodimers.}},
  url          = {{https://lup.lub.lu.se/search/files/3270794/4053649.pdf}},
  doi          = {{10.1371/journal.pone.0061832}},
  volume       = {{8}},
  year         = {{2013}},
}