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The E3 ubiquitin ligase mind bomb-2 (MIB2) protein controls B-cell CLL/lymphoma 10 (BCL10)-dependent NF-κB activation.

B-cell CLL/lymphoma 10 (BCL10) is crucial for the activation of NF-κB in numerous immune receptor signaling pathways, including the T-cell receptor (TCR) and B-cell receptor signaling pathways. However, the molecular mechanisms that lead to signal transduction from BCL10 to downstream NF-κB effector kinases, such as TAK1 and components of the IKK complex, are not entirely understood. Here we used a proteomic approach and identified the E3 ligase MIB2 as a novel component of the activated BCL10 complex. In vitro translation and pulldown assays suggest direct interaction between BCL10 and MIB2. Overexpression experiments show that MIB2 controls BCL10-mediated activation of NF-κB by promoting autoubiquitination and ubiquitination of IKKγ/NEMO, as well as recruitment and activation of TAK1. Knockdown of MIB2 inhibited BCL10-dependent NF-κB activation. Together, our results identify MIB2 as a novel component of the activated BCL10 signaling complex and a missing link in the BCL10-dependent NF-κB signaling pathway.

Pubmed ID: 21896478


  • Stempin CC
  • Chi L
  • Giraldo-Vela JP
  • High AA
  • Häcker H
  • Redecke V


The Journal of biological chemistry

Publication Data

October 28, 2011

Associated Grants

  • Agency: NIAID NIH HHS, Id: AI083443

Mesh Terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • HEK293 Cells
  • Humans
  • I-kappa B Kinase
  • Intracellular Signaling Peptides and Proteins
  • Jurkat Cells
  • MAP Kinase Kinase Kinases
  • Mice
  • NF-kappa B
  • Proteomics
  • Signal Transduction
  • Ubiquitin-Protein Ligases
  • Ubiquitination