@article{4764e23e4a074d68837dd20ab51c1878,
title = "Muscle-specific Cand2 is translationally upregulated by mTORC1 and promotes adverse cardiac remodeling",
abstract = "The mechanistic target of rapamycin (mTOR) promotes pathological remodeling in the heart by activating ribosomal biogenesis and mRNA translation. Inhibition of mTOR in cardiomyocytes is protective; however, a detailed role of mTOR in translational regulation of specific mRNA networks in the diseased heart is unknown. We performed cardiomyocyte genome-wide sequencing to define mTOR-dependent gene expression control at the level of mRNA translation. We identify the muscle-specific protein Cullin-associated NEDD8-dissociated protein 2 (Cand2) as a translationally upregulated gene, dependent on the activity of mTOR. Deletion of Cand2 protects the myocardium against pathological remodeling. Mechanistically, we show that Cand2 links mTOR signaling to pathological cell growth by increasing Grk5 protein expression. Our data suggest that cell-type-specific targeting of mTOR might have therapeutic value against pathological cardiac remodeling.",
keywords = "Cand2, cardiac, hypertrophy, mTOR",
author = "G{\'o}rska, {Agnieszka A.} and Clara Sandmann and Eva Riechert and Christoph Hofmann and Ellen Malovrh and Eshita Varma and Vivien Kmietczyk and Julie {\"O}lschl{\"a}ger and Lonny J{\"u}rgensen and Verena Kamuf-Schenk and Claudia Stroh and Jennifer Furkel and Konstandin, {Mathias H.} and Carsten Sticht and Etienne Boileau and Christoph Dieterich and Norbert Frey and Katus, {Hugo A.} and Shirin Doroudgar and Mirko V{\"o}lkers",
note = "Funding Information: A.A.G., H.A.K., M.V., S.D., and C.D. acknowledge the DZHK (German Centre for Cardiovascular Research) Partner Site Heidelberg/Mannheim. C.D. acknowledges funding from the Klaus-Tschira Stiftung GmbH. S.D. acknowledges the European Society of Cardiology Basic Research Fellowship and the DZHK Excellence Programme. M.V. acknowledges the DFG (German Research Foundation, DFG VO 1659 2/1, DFG VO 1659 2/2, DFG VO 1659 4/1, DFG VO 1659 6/1), the Boehringer Ingelheim Foundation (Plus 3 Programme). Open Access funding enabled and organized by Projekt DEAL. Funding Information: A.A.G., H.A.K., M.V., S.D., and C.D. acknowledge the DZHK (German Centre for Cardiovascular Research) Partner Site Heidelberg/Mannheim. C.D. acknowledges funding from the Klaus‐Tschira Stiftung GmbH. S.D. acknowledges the European Society of Cardiology Basic Research Fellowship and the DZHK Excellence Programme. M.V. acknowledges the DFG (German Research Foundation, DFG VO 1659 2/1, DFG VO 1659 2/2, DFG VO 1659 4/1, DFG VO 1659 6/1), the Boehringer Ingelheim Foundation (Plus 3 Programme). Open Access funding enabled and organized by Projekt DEAL. Publisher Copyright: {\textcopyright} 2021 The Authors. Published under the terms of the CC BY NC ND 4.0 license",
year = "2021",
month = dec,
day = "6",
doi = "10.15252/embr.202052170",
language = "English (US)",
volume = "22",
journal = "EMBO Reports",
issn = "1469-221X",
publisher = "Nature Publishing Group",
number = "12",
}