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.authorChen, Lena
dc.contributor.authorChoi, Catherine S.W.
dc.contributor.authorSanchez-Arias, Juan C.
dc.contributor.authorArbour, Laura T.
dc.contributor.authorSwayne, Leigh Anne
dc.date.accessioned2019-11-21T20:02:29Z
dc.date.available2019-11-21T20:02:29Z
dc.date.copyright2019en_US
dc.date.issued2019-11-21
dc.description.abstractAnkyrin-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.reviewstatusUnrevieweden_US
dc.description.scholarlevelFacultyen_US
dc.description.sponsorshipLC 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.identifier.urihttps://www.nrcresearchpress.com/journal/bcb
dc.identifier.urihttp://hdl.handle.net/1828/11325
dc.identifier.urihttps://doi.org/10.1139/bcb-2019-0082
dc.language.isoenen_US
dc.subjectAnkyrin-B
dc.subjectproteasome
dc.subjectcardiomyocytes
dc.subjectcell viability
dc.subjectIsland Medical Program
dc.subject.departmentDivision of Medical Sciences
dc.subject.departmentSchool of Medical Sciences
dc.titleAnkyrin-B p.S646F undergoes increased proteasome degradation and reduces cell viability in the H9c2 rat ventricular cardiomyoblast cell lineen_US
dc.typePreprinten_US

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