Monocyte Chemotactic Protein-induced Protein 1 and 4 Form a Complex but Act Independently in Regulation of Interleukin-6 mRNA Degradation

J Biol Chem. 2015 Aug 21;290(34):20782-20792. doi: 10.1074/jbc.M114.635870. Epub 2015 Jul 1.

Abstract

It was recently demonstrated that MCPIP1 is a critical factor that controls inflammation and immune homeostasis; however, the relationship between MCPIP1 and other members of this protein family is largely unknown. Here, we report that MCPIP1 interacts with MCPIP4 to form a protein complex, but acts independently in the regulation of IL-6 mRNA degradation. In an effort to identify MCPIP1-interacting proteins by co-immunoprecipitation (Co-IP) and mass-spec analysis, MCPIP4 was identified as a MCPIP1-interacting protein, which was further confirmed by Co-IP and mammalian two-hybrid assay. Immunofluorescence staining showed that MCPIP4 was co-localized with MCPIP1 in the GW-body, which features GW182 and Argonaute 2. Further studies showed that MCPIP1 and MCPIP4 act independently in regulation of IL-6 mRNA degradation. These results suggest that MCPIP1 and MCPIP4 may additively contribute to control IL-6 production in vivo.

Keywords: RNase; inflammation; interleukin; mRNA decay; protein domain; protein-protein interaction.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • COS Cells
  • Cell Cycle Proteins
  • Cell Line
  • Chlorocebus aethiops
  • Endonucleases
  • Endoribonucleases
  • Gene Expression Regulation
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Immunoprecipitation
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism*
  • Macrophages / cytology
  • Macrophages / metabolism*
  • Mice
  • Molecular Sequence Data
  • Plasmids / chemistry
  • Plasmids / metabolism
  • Protein Binding
  • Proteins / genetics
  • Proteins / metabolism*
  • RNA Stability / genetics*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Ribonucleases / genetics
  • Ribonucleases / metabolism*
  • Signal Transduction
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Two-Hybrid System Techniques

Substances

  • Cell Cycle Proteins
  • IL6 protein, human
  • Interleukin-6
  • Proteins
  • RNA, Messenger
  • Recombinant Proteins
  • Transcription Factors
  • Endonucleases
  • Endoribonucleases
  • Ribonucleases
  • ZC3H12A protein, human
  • ZC3H12D protein, human