Our hosting provider will be performing UPS maintenance on Tuesday, Oct 25, 2016 between 8 AM and 5 PM PDT. SciCrunch searching services will be down during this time.

Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

The ubiquitin-editing enzyme A20 restricts nucleotide-binding oligomerization domain containing 2-triggered signals.


Muramyl dipeptide (MDP), a product of bacterial cell-wall peptidoglycan, activates innate immune cells by stimulating nucleotide-binding oligomerization domain containing 2 (NOD2) -dependent activation of the transcription factor NFkappaB and transcription of proinflammatory genes. A20 is a ubiquitin-modifying enzyme that restricts tumor necrosis factor (TNF) receptor and Toll-like receptor (TLR) -induced signals. We now show that MDP induces ubiquitylation of receptor- interacting protein 2 (RIP2) in primary macrophages. A20-deficient cells exhibit dramatically amplified responses to MDP, including increased RIP2 ubiquitylation, prolonged NFkappaB signaling, and increased production of proinflammatory cytokines. In addition, in vivo responses to MDP are exaggerated in A20-deficient mice and in chimeric mice bearing A20-deficient hematopoietic cells. These exaggerated responses occur independently of the TLR adaptors MyD88 and TRIF as well as TNF signals. These findings indicate that A20 directly restricts NOD2 induced signals in vitro and in vivo, and provide new insights into how these signals are physiologically restricted.

Pubmed ID: 18342009


  • Hitotsumatsu O
  • Ahmad RC
  • Tavares R
  • Wang M
  • Philpott D
  • Turer EE
  • Lee BL
  • Shiffin N
  • Advincula R
  • Malynn BA
  • Werts C
  • Ma A



Publication Data

March 17, 2008

Associated Grants

  • Agency: NIDDK NIH HHS, Id: 5P30DK026743
  • Agency: NIDDK NIH HHS, Id: R01 DK052751

Mesh Terms

  • Acetylmuramyl-Alanyl-Isoglutamine
  • Animals
  • Cysteine Endopeptidases
  • Intracellular Signaling Peptides and Proteins
  • Macrophages
  • Mice
  • Mice, Mutant Strains
  • NF-kappa B
  • Nod2 Signaling Adaptor Protein
  • Receptor-Interacting Protein Serine-Threonine Kinases
  • Signal Transduction
  • Ubiquitin
  • Ubiquitination