@article { , title = {Do sodium channel proteolytic fragments regulate sodium channel expression?}, abstract = {© 2017 Taylor \& Francis The cardiac voltage-gated sodium channel (gene: SCN5A, protein: Na V 1.5) is responsible for the sodium current that initiates the cardiomyocyte action potential. Research into the mechanisms of SCN5A gene expression has gained momentum over the last few years. We have recently described the transcriptional regulation of SCN5A by GATA4 transcription factor. In this addendum to our study, we report our observations that 1) the linker between domains I and II (L DI-DII ) of Na V 1.5 contains a nuclear localization signal (residues 474–481) that is necessary to localize L DI-DII into the nucleus, and 2) nuclear L DI-DII activates the SCN5A promoter in gene reporter assays using cardiac-like H9c2 cells. Given that voltage-gated sodium channels are known targets of proteases such as calpain, we speculate that Na V 1.5 degradation is signaled to the cell transcriptional machinery via nuclear localization of L DI-DII and subsequent stimulation of the SCN5A promoter.}, doi = {10.1080/19336950.2017.1355663}, eissn = {1933-6969}, issn = {1933-6950}, issue = {5}, journal = {Channels}, pages = {476-481}, publicationstatus = {Published}, publisher = {Taylor and Francis}, url = {https://hull-repository.worktribe.com/output/520223}, volume = {11}, keyword = {Health and Health Inequalities, Voltage-gated sodium channel, Transcription factor, Gene expression, Nuclear localisation signal, Mutagenesis}, year = {2017}, author = {Onwuli, Donatus O. and Yañez-Bisbe, Laia and Pinsach-Abuin, Mel·lina and Tarradas, Anna and Brugada, Ramon and Greenman, John and Pagans, Sara and Beltran-Alvarez, Pedro} }