Abstract
The molecular complexes containing BCL10, MALT1 and CARMA proteins (CBM complex) have been recently identified as a key component in the signal transduction pathways that regulate activation of Nuclear Factor kappaB (NF-κB) transcription factor. Herein we identified the DEP domain-containing protein DEPDC7 as cellular binding partners of CARMA2 and CARMA3 proteins. DEPDC7 displays a cytosolic distribution and its expression induces NF-κB activation. Conversely, shRNA-mediated abrogation of DEPDC7 results in impaired NF-κB activation following G protein-coupled receptors stimulation, or stimuli that require CARMA2 and CARMA3, but not CARMA1. Thus, this study identifies DEPDC7 as a CARMA interacting molecule, and provides evidence that DEPDC7 may be required to specifically convey on the CBM complex signals coming from activated G protein-coupled receptors.
Highlights
The Nuclear Factor kappaB (NF-kB) signaling pathway is a major regulator of normal immune and inflammatory responses, cell proliferation, differentiation, apoptosis and oncogenesis [1].PLOS ONE | DOI:10.1371/journal.pone.0116062 December 26, 2014DEPDC7 Regulates NF-kB ActivationPrevious studies have demonstrated that signal-dependent formation of the CARMA-BCL10-MALT1 complex recruits downstream signaling components that modulate activation of NF-kB transcription factor [2,3,4]
Key component of the CBM complex are the three CARMA proteins, CARMA1, 2 and 3, which constitute a family of proteins conserved across many species and are characterized by the presence of different functional domains shared by all members of the family [2, 3]
To test for a physical association between CARMA2sh and DEPDC7 in mammalian cells, HEK-293 cells were cotransfected with plasmids expressing FLAG-tagged DEPDC7 together with a vector encoding for HA-tagged CARMA2sh or CARMA2cardless (CARMA2cl) (Fig. 1A)
Summary
The NF-kB signaling pathway is a major regulator of normal immune and inflammatory responses, cell proliferation, differentiation, apoptosis and oncogenesis [1].PLOS ONE | DOI:10.1371/journal.pone.0116062 December 26, 2014DEPDC7 Regulates NF-kB ActivationPrevious studies have demonstrated that signal-dependent formation of the CARMA-BCL10-MALT1 complex (known as the CBM complex) recruits downstream signaling components that modulate activation of NF-kB transcription factor [2,3,4]. Key component of the CBM complex are the three CARMA proteins, CARMA1, 2 and 3, which constitute a family of proteins conserved across many species and are characterized by the presence of different functional domains shared by all members of the family [2, 3]. CARMA1 is mostly expressed in lymphoid tissues [5], while CARMA2 and CARMA3 are non-overlappingly expressed in a variety of different tissues [6,7,8]. This characteristic expression pattern of CARMA protein has corroborated the speculation that they may perform similar functions in different tissues
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