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Ankyrin-B p.S646F undergoes increased proteasome degradation and reduces cell viability in the H9c2 rat ventricular cardiomyoblast cell line

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dc.contributor.author Chen, Lena
dc.contributor.author Choi, Catherine S.W.
dc.contributor.author Sanchez-Arias, Juan C.
dc.contributor.author Arbour, Laura T.
dc.contributor.author Swayne, Leigh Anne
dc.date.accessioned 2019-11-21T20:02:29Z
dc.date.available 2019-11-21T20:02:29Z
dc.date.copyright 2019 en_US
dc.date.issued 2019-11-21
dc.identifier.uri https://www.nrcresearchpress.com/journal/bcb
dc.identifier.uri http://hdl.handle.net/1828/11325
dc.identifier.uri https://doi.org/10.1139/bcb-2019-0082
dc.description.abstract Ankyrin-B (AnkB) is scaffolding protein that anchors integral membrane proteins to the cardiomyocyte cytoskeleton. We recently identified an AnkB variant, AnkB p.S646F (ANK2 c.1937 C>T) associated with a phenotype ranging from predisposition for cardiac arrhythmia to cardiomyopathy. AnkB p.S646F exhibited reduced expression levels in the H9c2 rat ventricular- derived cardiomyoblast cell line relative to wildtype AnkB. Here we demonstrate that AnkB is regulated by proteasomal degradation and proteasome inhibition rescues AnkB p.S646F expression levels in H9c2 cells, although this effect is not conserved with differentiation. We also compared the impact of wildtype AnkB and AnkB p.S646F on cell viability and proliferation. AnkB p.S646F expression resulted in decreased cell viability at 30 hours post-transfection, whereas we observed a greater proportion of cycling, Ki67-positive cells at 48 h post-transfection. Notably, the number of GFP-positive cells was low, and was consistent between wildtype AnkB and AnkB p.S646F expressing cells, suggesting that AnkB and AnkB p.S646F affected paracrine communication between H9c2 cells differentially. In summary, this work reveals AnkB levels are regulated by the proteasome, and that AnkB p.S646F compromises cell viability. Together these findings provide key new insights into the putative cellular and molecular mechanisms of AnkB-related cardiac disease. en_US
dc.description.sponsorship LC was supported by a Natural Sciences and Engineering Research Council of Canada CGS-M and University of Victoria graduate scholarships. LAS is supported by the Michael Smith Foundation for Health Research & BC Schizophrenia Society Foundation Scholar award. This research was funded by the University of Victoria seed funds to LAS, and CIHR funding (PJT-153392) awarded to LTA and LAS. en_US
dc.language.iso en en_US
dc.subject Ankyrin-B en_US
dc.subject proteasome en_US
dc.subject cardiomyocytes en_US
dc.subject cell viability en_US
dc.title Ankyrin-B p.S646F undergoes increased proteasome degradation and reduces cell viability in the H9c2 rat ventricular cardiomyoblast cell line en_US
dc.type Preprint en_US
dc.description.scholarlevel Faculty en_US
dc.description.reviewstatus Unreviewed en_US


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