Probes to monitor activity of the paracaspase MALT1

Chem Biol. 2015 Jan 22;22(1):139-47. doi: 10.1016/j.chembiol.2014.11.011. Epub 2014 Dec 31.

Abstract

The human paracaspase mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) plays a central role in nuclear factor-κB (NF-κB) signaling as both a protease and scaffolding protein. Knocking out MALT1 leads to impaired NF-κB signaling and failure to mount an effective immune response. However, it is unclear to which degree it is the scaffolding function versus the proteolytic activity of MALT1 that is essential. Previous work involving a MALT1 inhibitor with low selectivity suggests that the enzymatic function plays an important role in different cell lines. To help elucidate this proteolytic role of MALT1, we have designed activity-based probes that inhibit its proteolytic activity. The probes selectively label active enzyme and can be used to inhibit MALT1 and trace its activity profile, helping to create a better picture of the significance of the proteolytic function of MALT1.

Publication types

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

MeSH terms

  • Caspases / chemistry
  • Caspases / genetics
  • Caspases / metabolism*
  • Cell Line, Tumor
  • HEK293 Cells
  • Humans
  • Kinetics
  • Molecular Probes / chemistry
  • Molecular Probes / metabolism*
  • Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein
  • Mutation
  • NF-kappa B / metabolism
  • Neoplasm Proteins / chemistry
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Protein Binding
  • Proteolysis
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Signal Transduction
  • Transfection

Substances

  • Molecular Probes
  • NF-kappa B
  • Neoplasm Proteins
  • Recombinant Proteins
  • Caspases
  • MALT1 protein, human
  • Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein