Searching across hundreds of databases

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

X
Forgot Password

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

X
Forgot Password

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

MCP-induced protein 1 deubiquitinates TRAF proteins and negatively regulates JNK and NF-kappaB signaling.

The intensity and duration of macrophage-mediated inflammatory responses are controlled by proteins that modulate inflammatory signaling pathways. MCPIP1 (monocyte chemotactic protein-induced protein 1), a recently identified CCCH Zn finger-containing protein, plays an essential role in controlling macrophage-mediated inflammatory responses. However, its mechanism of action is poorly understood. In this study, we show that MCPIP1 negatively regulates c-Jun N-terminal kinase (JNK) and NF-κB activity by removing ubiquitin moieties from proteins, including TRAF2, TRAF3, and TRAF6. MCPIP1-deficient mice spontaneously developed fatal inflammatory syndrome. Macrophages and splenocytes from MCPIP1(-/-) mice showed elevated expression of inflammatory gene expression, increased JNK and IκB kinase activation, and increased polyubiquitination of TNF receptor-associated factors. In vitro assays directly demonstrated the deubiquitinating activity of purified MCPIP1. Sequence analysis together with serial mutagenesis defined a deubiquitinating enzyme domain and a ubiquitin association domain in MCPIP1. Our results indicate that MCPIP1 is a critical modulator of inflammatory signaling.

Pubmed ID: 21115689 RIS Download

Mesh terms: Animals | Cell Line | Cells, Cultured | Embryo, Mammalian | Female | Fibroblasts | Gene Expression Profiling | HEK293 Cells | Humans | Immunoblotting | Interleukin-1beta | JNK Mitogen-Activated Protein Kinases | Lipopolysaccharides | Macrophages | Male | Mice | Mice, Inbred C57BL | Mice, Knockout | NF-kappa B | Protein Binding | Ribonucleases | Signal Transduction | Tumor Necrosis Factor Receptor-Associated Peptides and Proteins | Ubiquitin | Ubiquitination

Research resources used in this publication

None found

Research tools detected in this publication

Data used in this publication

Associated grants

  • Agency: NHLBI NIH HHS, Id: R21 HL098794
  • Agency: NHLBI NIH HHS, Id: HL084456
  • Agency: NHLBI NIH HHS, Id: HL69458
  • Agency: NHLBI NIH HHS, Id: HL085499
  • Agency: NHLBI NIH HHS, Id: R21 HL098794-01A1
  • Agency: NHLBI NIH HHS, Id: R56 HL069458
  • Agency: NHLBI NIH HHS, Id: R01 HL069458
  • Agency: NHLBI NIH HHS, Id: R01 HL085499
  • Agency: NHLBI NIH HHS, Id: R01 HL084456

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

This is a list of tools and resources that we have found mentioned in this publication.