AIP augments CARMA1-BCL10-MALT1 complex formation to facilitate NF-κB signaling upon T cell activation

Cell Commun Signal. 2014 Jul 22;12:49. doi: 10.1186/s12964-014-0049-7.

Abstract

Background: The CARMA1-BCL10-MALT1 (CBM) complex bridges T cell receptor (TCR) signaling to the canonical IκB kinase (IKK)/NF-κB pathway. The CBM complex constitutes a signaling cluster of more than 1 Mio Dalton. Little is known about factors that facilitate the rapid assembly and maintenance of this dynamic higher order complex.

Findings: Here, we report the novel interaction of the aryl hydrocarbon receptor (AHR) interacting protein (AIP) and the molecular scaffold protein CARMA1. In T cells, transient binding of CARMA1 and AIP enhanced formation of the CBM complex. Thereby, AIP promoted optimal IKK/NF-κB signaling and IL-2 production in response to TCR/CD28 co-stimulation.

Conclusions: Our data demonstrate that AIP acts as a positive regulator of NF-κB signaling upon T cell activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • B-Cell CLL-Lymphoma 10 Protein
  • CARD Signaling Adaptor Proteins / metabolism*
  • CD28 Antigens / metabolism
  • Caspases / metabolism*
  • Cell Line, Tumor
  • Guanylate Cyclase / metabolism*
  • Humans
  • I-kappa B Kinase / metabolism
  • Interleukin-2 / metabolism
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Lymph Nodes / cytology
  • Mice
  • Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein
  • Multiprotein Complexes / metabolism
  • NF-kappa B / metabolism*
  • Neoplasm Proteins / metabolism*
  • Primary Cell Culture
  • Signal Transduction*
  • Spleen / cytology
  • T-Lymphocytes / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • B-Cell CLL-Lymphoma 10 Protein
  • BCL10 protein, human
  • CARD Signaling Adaptor Proteins
  • CD28 Antigens
  • Interleukin-2
  • Intracellular Signaling Peptides and Proteins
  • Multiprotein Complexes
  • NF-kappa B
  • Neoplasm Proteins
  • aryl hydrocarbon receptor-interacting protein
  • I-kappa B Kinase
  • Caspases
  • MALT1 protein, human
  • Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein
  • CARD11 protein, human
  • Guanylate Cyclase