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Alternative splicing of CARMA2/CARD14 transcripts generates protein variants with differential effect on NF‐κB activation and endoplasmic reticulum stress‐induced cell death
Author(s) -
Scudiero Ivan,
Zotti Tiziana,
Ferravante Angela,
Vessichelli Mariangela,
Vito Pasquale,
Stilo Romania
Publication year - 2011
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.22667
Subject(s) - rna splicing , pdz domain , biology , alternative splicing , endoplasmic reticulum , microbiology and biotechnology , transcription factor , signal transduction , gene isoform , coiled coil , gene , genetics , rna
The caspase recruitment domain (CARD)‐containing proteins CARMA1‐3 share high degree of sequence, structure and functional homology. Whereas CARMA1 and CARMA3 have been identified as crucial components of signal transduction pathways that lead to activation of NF‐κB transcription factor, little is known about the function of CARMA2. Here we report the identification of two splice variants of CARMA2. One transcript, named CARMA2 short (CARMA2 sh ), is predicted to encode for a CARMA2 polypeptide containing the CARD, coiled coil, and a PDZ domains, but lacking the SH3 and the GuK domains. The second variant, CARMA2 cardless (CARMA2 cl ), encodes for a polypeptide lacking the CARD domain and containing only a portion of the coiled coil domain and a linker region. Expression analysis confirmed the presence of the CARMA2 alternatively spliced transcripts in both human cell lines and tissues. Fluorescence microscopy data show that both splice variants localize in the cytosol. Biochemical experiments indicate that CARMA2 sh interacts with TRAF2 and activates NF‐κB in a TRAF2‐dependent manner. Finally, CARMA2 sh variant protects cells from apoptosis induced by different stimuli. Taken together, these results demonstrate that multiple transcripts encoding several CARMA2 isoforms exist in vivo and regulate NF‐κB activation and apoptosis. J. Cell. Physiol. 226: 3121–3131, 2011. © 2011 Wiley Periodicals, Inc.