Acetylation of MKP-1 and the Control of Inflammation

Sci. Signal., 14 October 2008
Vol. 1, Issue 41, p. pe44
DOI: 10.1126/scisignal.141pe44

Acetylation of MKP-1 and the Control of Inflammation

  1. Hongbo Chi1,* and
  2. Richard A. Flavell2,3,*
  1. 1Department of Immunology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA.
  2. 2Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520, USA.
  3. 3Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
  1. *Corresponding authors. E-mail: hongbo.chi{at} (H.C.); richard.flavell{at} (R.A.F.)


Innate immune responses mediated by Toll-like receptors (TLRs), a class of pattern-recognition receptors, play a critical role in the defense against microbial pathogens. However, excessive TLR-mediated responses result in sepsis, autoimmunity, and chronic inflammation. To prevent deleterious activation of TLRs, cells have evolved multiple mechanisms that inhibit innate immune reactions. Stimulation of TLRs induces the expression of the gene encoding the mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1), a nuclear-localized dual-specificity phosphatase that preferentially dephosphorylates p38 MAPK and c-Jun N-terminal kinase (JNK), resulting in the attenuation of TLR-triggered production of proinflammatory cytokines. MKP-1 is posttranslationally modified by multiple mechanisms, including phosphorylation. A study now demonstrates that MKP-1 is also acetylated on a key lysine residue following stimulation of TLRs. Acetylation of MKP-1 promotes the interaction of MKP-1 with its substrate p38 MAPK, which results in dephosphorylation of p38 MAPK and the inhibition of innate immunity.


H. Chi and R. A. Flavell, Acetylation of MKP-1 and the Control of Inflammation. Sci. Signal. 1, pe44 (2008).

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