Display Settings:

Format

Send to:

Choose Destination
Mol Biol Cell. 2013 Sep;24(18):2966-80. doi: 10.1091/mbc.E13-02-0113. Epub 2013 Jul 17.

Calpain A modulates toll responses by limited Cactus/IκB proteolysis.

Author information

  • 1Institute for Biomedical Sciences, Federal University of Rio de Janeiro, CEP 21941-902 Rio de Janeiro, Brazil Chemistry Institute, Federal University of Rio de Janeiro, CEP 21941-902 Rio de Janeiro, Brazil Instituto Nacional de Ciência e Tecnologia em Entomologia Molecular, Rio de Janeiro, Brazil Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544 Princeton Collaborative Proteomics and Mass Spectrometry Center, Princeton University, Princeton, NJ 08544 Molecular Biology Department, Princeton University, Princeton, NJ 08544 Howard Hughes Medical Institute, Chevy Chase, MD 20815.

Abstract

Calcium-dependent cysteine proteases of the calpain family are modulatory proteases that cleave their substrates in a limited manner. Among their substrates, calpains target vertebrate and invertebrate IκB proteins. Because proteolysis by calpains potentially generates novel protein functions, it is important to understand how this affects NFκB activity. We investigate the action of Calpain A (CalpA) on the Drosophila melanogaster IκB homologue Cactus in vivo. CalpA alters the absolute amounts of Cactus protein. Our data indicate, however, that CalpA uses additional mechanisms to regulate NFκB function. We provide evidence that CalpA interacts physically with Cactus, recognizing a Cactus pool that is not bound to Dorsal, a fly NFκB/Rel homologue. We show that proteolytic cleavage by CalpA generates Cactus fragments lacking an N-terminal region required for Toll responsiveness. These fragments are generated in vivo and display properties distinct from those of full-length Cactus. We propose that CalpA targets free Cactus, which is incorporated into and modulates Toll-responsive complexes in the embryo and immune system.

PMID:
23864715
[PubMed - in process]
PMCID:
PMC3771957
Free PMC Article

Images from this publication.See all images (8)Free text

FIGURE 1:
FIGURE 2:
FIGURE 3:
FIGURE 4:
FIGURE 5:
FIGURE 6:
FIGURE 7:
FIGURE 8:
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk