{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T10:06:39Z","timestamp":1790244399603,"version":"4.1.0"},"reference-count":53,"publisher":"Wiley","issue":"53","license":[{"start":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:00:00Z","timestamp":1782691200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:00:00Z","timestamp":1782691200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82471913"],"award-info":[{"award-number":["82471913"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82192882"],"award-info":[{"award-number":["82192882"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Pathological cardiac hypertrophy drives heart failure progression, but the proteostatic mechanisms restraining maladaptive remodeling remain poorly defined. Here, we identify Zyg\u201011\u2010related regulator 1 (ZER1) as a previously unrecognized Gly\/N\u2010degron proteostatic regulator of pressure overload\u2010induced remodeling. Failing human hearts and mouse transverse aortic constriction (TAC) hearts show suppression of a CRL2\/Gly\u2010N\u2010degron signature and reduced ZER1 abundance. Global and cardiomyocyte\u2010specific\n                    <jats:italic>Zer1<\/jats:italic>\n                    loss exacerbates TAC\u2010induced hypertrophy, fibrosis, and systolic dysfunction. Mechanistically, ZER1 directly binds disheveled segment polarity protein 2 (DVL2) in an N\u2010terminus\u2010dependent manner and promotes its K48\u2010linked polyubiquitination and proteasomal degradation, thereby limiting DVL2 accumulation and downstream CaMKII\u2010HDAC4\u2010MEF2C signaling. Cardiomyocyte\u2010targeted\n                    <jats:italic>Dvl2<\/jats:italic>\n                    knockdown abolishes the phenotypic differences between\n                    <jats:italic>Zer1<\/jats:italic>\n                    <jats:sup>fl\/fl<\/jats:sup>\n                    and\n                    <jats:italic>Zer1<\/jats:italic>\n                    \u2010cKO mice after TAC. WWP1 knockdown cannot rescue the phenotype induced by ZER1 deletion, demonstrating that ZER1 is required for\n                    <jats:italic>Wwp1<\/jats:italic>\n                    knockdown\u2010mediated protection against pressure overload\u2010induced cardiac remodeling. Importantly, cardiomyocyte\u2010selective AAV9\u2010mediated restoration of ZER1 after TAC onset attenuates established remodeling and preserves cardiac function. Together, these findings define a ZER1\u2010DVL2 proteostatic checkpoint that links Gly\/N\u2010degron\u2010dependent protein quality control to pathological cardiac remodeling and highlights ZER1 as a potential therapeutic target for heart failure.\n                  <\/jats:p>","DOI":"10.1002\/advs.76308","type":"journal-article","created":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T16:51:07Z","timestamp":1782751867000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["ZER1 Restrains Pressure Overload\u2010Induced Cardiac Remodeling by Targeting DVL2 for Gly\/N\u2010Degron\u2010Dependent Degradation"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3462-6493","authenticated-orcid":false,"given":"Mingchao","family":"Jiang","sequence":"first","affiliation":[{"name":"Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health) Wenzhou Medical 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