The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
Acetylation of mitogen-activated protein kinase phosphatase-1 inhibits Toll-like receptor signaling
Open accessAbstract
The mitogen-activated protein kinase (MAPK) pathway plays a critical role in Toll-like receptor (TLR) signaling. MAPK phosphatase-1 (MKP-1) inhibits the MAPK pathway and decreases TLR signaling, but the regulation of MKP-1 is not completely understood. We now show that MKP-1 is acetylated, and that acetylation regulates its ability to interact with its substrates and deactivate inflammatory signaling. We found that LPS activates acetylation of MKP-1. MKP-1 is acetylated by p300 on lysine residue K57 within its substrate-binding domain. Acetylation of MKP-1 enhances its interaction with p38, thereby increasing its phosphatase activity and interrupting MAPK signaling. Inhibition of deacetylases increases MKP-1 acetylation and blocks MAPK signaling in wild-type (WT) cells; however, deacetylase inhibitors have no effect in cells lacking MKP-1. Furthermore, histone deacetylase inhibitors reduce inflammation and mortality in WT mice treated with LPS, but fail to protect MKP-1 knockout mice. Our data suggest that acetylation of MKP-1 inhibits innate immune signaling. This pathway may be an important therapeutic target in the treatment of inflammatory diseases.
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Regulation of activity of the transcription factor GATA-1 by acetylation
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MAP kinase phosphatase 1 controls innate immune responses and suppresses endotoxic shock
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Cited by
Functions and mechanisms of non-histone protein acetylation
Narita, T., Weinert, B. T., & Choudhary, C. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0081-3 · Cited by 1,232
Dual‐specificity MAP kinase phosphatases (MKPs): Shaping the outcome of MAP kinase signalling
Caunt, C. J., & Keyse, S. M. (2013) · The FEBS Journal · doi:10.1111/j.1742-4658.2012.08716.x · Cited by 535
Histone deacetylases as regulators of inflammation and immunity
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Metadata
- Authors
- Cao, W., Bao, C., Padalko, E., & Lowenstein, C. J.
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2008-05-26
- Volume
- 205
- Issue
- 6
- Pages
- 1491-1503
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- OpenAlex
- W2100587126
- Cited by
- 190
- References
- 9
- FWCI
- 6.82
- Type
- journal article
- Language
- en
- Open access
- green
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- Cao, W., Bao, C., Padalko, E., & Lowenstein, C. J. (2008). Acetylation of mitogen-activated protein kinase phosphatase-1 inhibits Toll-like receptor signaling. The Journal of Experimental Medicine. https://doi.org/10.1084/jem.20071728
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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