{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T22:58:55Z","timestamp":1780527535717,"version":"3.54.1"},"reference-count":60,"publisher":"American Society for Clinical Investigation","issue":"11","funder":[{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"crossref","award":["15PRE25090023"],"award-info":[{"award-number":["15PRE25090023"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"crossref","award":["Undergraduate Student Research Fellowship"],"award-info":[{"award-number":["Undergraduate Student Research Fellowship"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100008456","name":"A. Alfred Taubman Medical Research Institute","doi-asserted-by":"crossref","award":["Taubman Scholar Grant"],"award-info":[{"award-number":["Taubman Scholar Grant"]}],"id":[{"id":"10.13039\/100008456","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"crossref","award":["HL131327-01"],"award-info":[{"award-number":["HL131327-01"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"crossref","award":["R01 HL093338-01"],"award-info":[{"award-number":["R01 HL093338-01"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"crossref","award":["5R01 GM094231"],"award-info":[{"award-number":["5R01 GM094231"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"crossref","award":["R01 NS059690"],"award-info":[{"award-number":["R01 NS059690"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"crossref"}]},{"name":"The Children\u2019s Cardiomyopathy Foundation"},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"crossref","award":["Grant-in-Aid"],"award-info":[{"award-number":["Grant-in-Aid"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"crossref"}]},{"name":"The Lefkofsky Foundation","award":["Lefkofsky Scholar Award"],"award-info":[{"award-number":["Lefkofsky Scholar Award"]}]},{"DOI":"10.13039\/100007270","name":"University of Michigan","doi-asserted-by":"crossref","award":["Protein Folding Diseases Initiative"],"award-info":[{"award-number":["Protein Folding Diseases Initiative"]}],"id":[{"id":"10.13039\/100007270","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,6,7]]},"abstract":"<jats:p>\n                    Cardiac myosin binding protein C (\n                    <jats:italic>MYBPC3<\/jats:italic>\n                    ) is the most commonly mutated gene associated with hypertrophic cardiomyopathy (HCM). Haploinsufficiency of full-length MYBPC3 and disruption of proteostasis have both been proposed as central to HCM disease pathogenesis. Discriminating the relative contributions of these 2 mechanisms requires fundamental knowledge of how turnover of WT and mutant MYBPC3 proteins is regulated. We expressed several disease-causing mutations in MYBPC3 in primary neonatal rat ventricular cardiomyocytes. In contrast to WT MYBPC3, mutant proteins showed reduced expression and failed to localize to the sarcomere. In an unbiased coimmunoprecipitation\/mass spectrometry screen, we identified HSP70-family chaperones as interactors of both WT and mutant MYBPC3. Heat shock cognate 70 kDa (HSC70) was the most abundant chaperone interactor. Knockdown of HSC70 significantly slowed degradation of both WT and mutant MYBPC3, while pharmacologic activation of HSC70 and HSP70 accelerated degradation. HSC70 was expressed in discrete striations in the sarcomere. Expression of mutant MYBPC3 did not affect HSC70 localization, nor did it induce a protein folding stress response or ubiquitin proteasome dysfunction. Together these data suggest that WT and mutant MYBPC3 proteins are clients for HSC70, and that the HSC70 chaperone system plays a major role in regulating MYBPC3 protein turnover.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.99319","type":"journal-article","created":{"date-parts":[[2018,6,6]],"date-time":"2018-06-06T11:01:10Z","timestamp":1528282870000},"source":"Crossref","is-referenced-by-count":35,"title":["HSC70 is a chaperone for wild-type and mutant cardiac myosin binding protein C"],"prefix":"10.1172","volume":"3","author":[{"given":"Amelia A.","family":"Glazier","sequence":"first","affiliation":[{"name":"Department of Molecular and Integrative Physiology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neha","family":"Hafeez","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8221-7673","authenticated-orcid":true,"given":"Dattatreya","family":"Mellacheruvu","sequence":"additional","affiliation":[{"name":"Department of Computational Medicine and Bioinformatics,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Venkatesha","family":"Basrur","sequence":"additional","affiliation":[{"name":"Department of Pathology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexey I.","family":"Nesvizhskii","sequence":"additional","affiliation":[{"name":"Department of Computational Medicine and Bioinformatics,"},{"name":"Department of Pathology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2506-4329","authenticated-orcid":true,"given":"Lap Man","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering, University of Michigan, Ann Arbor, Michigan, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Shao","sequence":"additional","affiliation":[{"name":"Institute for Neurodegenerative Diseases, UCSF, San Francisco, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6079-9756","authenticated-orcid":true,"given":"Vi","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Molecular and Integrative Physiology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaime M.","family":"Yob","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason E.","family":"Gestwicki","sequence":"additional","affiliation":[{"name":"Institute for Neurodegenerative Diseases, UCSF, San Francisco, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam S.","family":"Helms","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharlene M.","family":"Day","sequence":"additional","affiliation":[{"name":"Department of Molecular and Integrative Physiology,"},{"name":"Department of Internal Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2018,6,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2014.205"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1223602"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1007\/s10741-005-5253-5"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.109.202440"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.108.838672"},{"issue":"6\u20138","key":"B6","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/s10974-009-9174-0","article-title":"From genotype to phenotype: a longitudinal study of a patient with hypertrophic cardiomyopathy due to a mutation in the MYBPC3 gene","volume":"29","author":"Jacques","year":"2008","journal-title":"J Muscle Res Cell Motil"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.109.201251"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGENETICS.113.000448"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2005.01.004"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-011-0235-3"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1007\/s10974-011-9273-6"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.109.904557"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2015.08.020"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1106180"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2013.12.015"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1007\/s11906-009-0069-7"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvp309"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2013.12.016"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1172\/JCI45709"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2006.01.154"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.100.5.461"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2011.01.016"},{"key":"B23","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1007\/128_2012_323","article-title":"Allostery in the Hsp70 chaperone proteins","volume":"328","author":"Zuiderweg","year":"2013","journal-title":"Top Curr Chem"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1379\/1466-1268(2003)008<0303:CALBTC>2.0.CO;2"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.105.598409"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2012.07.014"},{"issue":"Pt 4","key":"B27","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1242\/jcs.00899","article-title":"Chaperone-mediated folding and assembly of myosin in striated muscle","volume":"117","author":"Srikakulam","year":"2004","journal-title":"J Cell Sci"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.110.225649"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2009.11.022"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2016.90"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2557"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.1140"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.01267.2001"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2004.05.032"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00590.2004"},{"issue":"Pt 1","key":"B36","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1042\/BJ20050412","article-title":"Heat-shock cognate 70 is required for the activation of heat-shock factor 1 in mammalian cells","volume":"392","author":"Ahn","year":"2005","journal-title":"Biochem J"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.111.963702"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1529\/biophysj.105.078147"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2012.03.009"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00249.2012"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1113\/JP273607"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2013.10.015"},{"issue":"14","key":"B43","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.94623","article-title":"A BAG3 chaperone complex maintains cardiomyocyte function during proteotoxic stress","volume":"2","author":"Judge","year":"2017","journal-title":"JCI Insight"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.4161\/auto.29409"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.4161\/cib.24925"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000148825.99184.50"},{"issue":"5","key":"B47","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1007\/s00418-004-0711-z","article-title":"Comparison of the small heat shock proteins alphaB-crystallin, MKBP, HSP25, HSP20, and cvHSP in heart and skeletal muscle","volume":"122","author":"Golenhofen","year":"2004","journal-title":"Histochem Cell Biol"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.96.12.4343"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.47.33235"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00601.2011"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201306077"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchf.2014.08.003"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.112.134932"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.1500511"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2012.08.045"},{"key":"B56","article-title":"A statistical model-building perspective to identification of MS\/MS spectra with PeptideProphet","volume":"13 Suppl 16","author":"Ma","year":"2012","journal-title":"BMC Bioinformatics"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.201000650"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000012222.70819.64"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/29.9.e45"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.115.020086"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/99319\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T12:59:54Z","timestamp":1779195594000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/99319"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,6,7]]},"references-count":60,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2018,6,7]]},"published-print":{"date-parts":[[2018,6,7]]}},"alternative-id":["10.1172\/jci.insight.99319"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.99319","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,6,7]]},"article-number":"e99319"}}