Abstract
The complexes formed by BCL10, MALT1 and members of the family of CARMA proteins have recently been the focus of much attention because they represent a key mechanism for regulating activation of the transcription factor NF-κB. Here, we report the functional characterization of a novel isoform of BCL10 in the trout Oncorhynchus mykiss, which we named tBCL10. tBCL10 dimerizes, binds to components of the CBM complex and forms cytoplasmic filaments. Functionally, tBCL10 activates NF-κB transcription factor and is inhibited by the deubiquitinating enzyme A20. Finally, depletion experiments indicate that tBCL10 can functionally replace the human protein. This work demonstrates the evolutionary conservation of the mechanism of NF-κB activation through the CBM complex, and indicates that the rainbow trout O. mykiss can serve as a model organism to study this pathway.
Highlights
The NF-jB family of transcription factors is a group of evolutionarily conserved proteins that are important regulators of the immune system function, controlling the expression of numerous proteins involved in innate and adaptive immunity [1,2]
The human Caspase recruiting domain (CARD)-containing protein BCL10 is a 233 amino acids protein originally identified as a target of translocation in a subset of mucosa-associated lymphoid tissue (MALT) lymphoma cells [3,4,5]
The three CARMA proteins, CARMA1, 2 and 3, 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 [8]
Summary
The NF-jB family of transcription factors is a group of evolutionarily conserved proteins that are important regulators of the immune system function, controlling the expression of numerous proteins involved in innate and adaptive immunity [1,2]. The three CARMA proteins, CARMA1, 2 and 3, 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 [8]. Because of multiple whole-genome duplications occurred in salmonid species [13], for the rainbow trout genome have been annotated four different genes encoding for putative proteins that share aminoacidic similarity with human BCL10. It is not established whether any of these genes is expressed, and no functional data is available regarding any of these proteins. Mazzone et al / FEBS Open Bio 5 (2015) 175–181 characterization of a rainbow trout O. mykiss BCL10 ortholog, defined tBCL10
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