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...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article (Journal) |
| Language: | English |
| Published: |
4 October 2021
|
| In: |
EMBO reports
Year: 2021, Volume: 22, Issue: 12, Pages: 1-19 |
| ISSN: | 1469-3178 |
| DOI: | 10.15252/embr.202052170 |
| Online Access: | Verlag, kostenfrei, Volltext: https://doi.org/10.15252/embr.202052170 Verlag, kostenfrei, Volltext: https://www.embopress.org/doi/full/10.15252/embr.202052170 
|
| Author Notes: | Agnieszka A Górska, Clara Sandmann, Eva Riechert, Christoph Hofmann, Ellen Malovrh, Eshita Varma, Vivien Kmietczyk, Julie Ölschläger, Lonny Jürgensen, Verena Kamuf-Schenk, Claudia Stroh, Jennifer Furkel, Mathias H Konstandin, Carsten Sticht, Etienne Boileau, Christoph Dieterich, Norbert Frey, Hugo A Katus, Shirin Doroudgar & Mirko Völkers |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1850820937 | ||
| 003 | DE-627 | ||
| 005 | 20230707004508.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 230622s2021 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.15252/embr.202052170 |2 doi | |
| 035 | |a (DE-627)1850820937 | ||
| 035 | |a (DE-599)KXP1850820937 | ||
| 035 | |a (OCoLC)1389536626 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Górska, Aga |e VerfasserIn |0 (DE-588)1164508989 |0 (DE-627)1028942818 |0 (DE-576)51005773X |4 aut | |
| 245 | 1 | 0 | |a Muscle-specific Cand2 is translationally upregulated by mTORC1 and promotes adverse cardiac remodeling |c Agnieszka A Górska, Clara Sandmann, Eva Riechert, Christoph Hofmann, Ellen Malovrh, Eshita Varma, Vivien Kmietczyk, Julie Ölschläger, Lonny Jürgensen, Verena Kamuf-Schenk, Claudia Stroh, Jennifer Furkel, Mathias H Konstandin, Carsten Sticht, Etienne Boileau, Christoph Dieterich, Norbert Frey, Hugo A Katus, Shirin Doroudgar & Mirko Völkers |
| 264 | 1 | |c 4 October 2021 | |
| 300 | |a 19 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Gesehen am 22.06.2023 | ||
| 520 | |a 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. | ||
| 650 | 4 | |a Cand2 | |
| 650 | 4 | |a cardiac | |
| 650 | 4 | |a hypertrophy | |
| 650 | 4 | |a mTOR | |
| 700 | 1 | |a Sandmann, Clara |d 1994- |e VerfasserIn |0 (DE-588)1194474667 |0 (DE-627)1676477071 |4 aut | |
| 700 | 1 | |a Riechert, Eva |d 1988- |e VerfasserIn |0 (DE-588)1192937465 |0 (DE-627)1671457323 |4 aut | |
| 700 | 1 | |a Sandmann, Christoph |d 1996- |e VerfasserIn |0 (DE-588)1167970926 |0 (DE-627)1031667733 |0 (DE-576)511376227 |4 aut | |
| 700 | 1 | |a Malovrh, Ellen |d 1992- |e VerfasserIn |0 (DE-588)1181722845 |0 (DE-627)1662363095 |4 aut | |
| 700 | 1 | |a Varma, Eshita |d 1992- |e VerfasserIn |0 (DE-588)121922314X |0 (DE-627)1735160954 |4 aut | |
| 700 | 1 | |a Kmietczyk, Vivien |d 1988- |e VerfasserIn |0 (DE-588)1194474799 |0 (DE-627)167649281X |4 aut | |
| 700 | 1 | |a Ölschläger, Julie |d 1997- |e VerfasserIn |0 (DE-588)129353207X |0 (DE-627)1850815615 |4 aut | |
| 700 | 1 | |a Jürgensen, Lonny |e VerfasserIn |0 (DE-588)1074309189 |0 (DE-627)831992107 |0 (DE-576)442582455 |4 aut | |
| 700 | 1 | |a Kamuf-Schenk, Verena |e VerfasserIn |0 (DE-588)1252339836 |0 (DE-627)1793496994 |4 aut | |
| 700 | 1 | |a Stroh, Claudia |e VerfasserIn |0 (DE-588)1293532800 |0 (DE-627)1850817790 |4 aut | |
| 700 | 1 | |a Furkel, Jennifer |d 1993- |e VerfasserIn |0 (DE-588)1219456640 |0 (DE-627)1735368377 |4 aut | |
| 700 | 1 | |a Konstandin, Mathias |d 1976- |e VerfasserIn |0 (DE-588)12390708X |0 (DE-627)706469240 |0 (DE-576)29393701X |4 aut | |
| 700 | 1 | |a Sticht, Carsten |d 1972- |e VerfasserIn |0 (DE-588)1020115718 |0 (DE-627)691110077 |0 (DE-576)250042177 |4 aut | |
| 700 | 1 | |a Boileau, Etienne |e VerfasserIn |0 (DE-588)1194473482 |0 (DE-627)1676464018 |4 aut | |
| 700 | 1 | |a Dieterich, Christoph |d 1975- |e VerfasserIn |0 (DE-588)130054844 |0 (DE-627)494359269 |0 (DE-576)297972448 |4 aut | |
| 700 | 1 | |a Frey, Norbert |e VerfasserIn |0 (DE-588)141244976 |0 (DE-627)625824075 |0 (DE-576)322969514 |4 aut | |
| 700 | 1 | |a Katus, Hugo |d 1951- |e VerfasserIn |0 (DE-588)108916618 |0 (DE-627)577155040 |0 (DE-576)289625076 |4 aut | |
| 700 | 1 | |a Doroudgar, Shirin |e VerfasserIn |0 (DE-588)1139390260 |0 (DE-627)897138023 |0 (DE-576)493250972 |4 aut | |
| 700 | 1 | |a Völkers, Mirko |d 1978- |e VerfasserIn |0 (DE-588)133026442 |0 (DE-627)530939932 |0 (DE-576)299573753 |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |a European Molecular Biology Organization |t EMBO reports |d [London] : Nature Publishing Group UK, 2000 |g 22(2021), 12, Artikel-ID e52170, Seite 1-19 |h Online-Ressource |w (DE-627)320645622 |w (DE-600)2025376-X |w (DE-576)095092153 |x 1469-3178 |7 nnas |
| 773 | 1 | 8 | |g volume:22 |g year:2021 |g number:12 |g elocationid:e52170 |g pages:1-19 |g extent:19 |a Muscle-specific Cand2 is translationally upregulated by mTORC1 and promotes adverse cardiac remodeling |
| 856 | 4 | 0 | |u https://doi.org/10.15252/embr.202052170 |x Verlag |x Resolving-System |z kostenfrei |3 Volltext |
| 856 | 4 | 0 | |u https://www.embopress.org/doi/full/10.15252/embr.202052170 |x Verlag |z kostenfrei |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20230622 | ||
| 992 | |a 20230622 | ||
| 993 | |a Article | ||
| 993 | |a Article | ||
| 994 | |a 2021 | ||
| 994 | |a 2021 | ||
| 998 | |g 133026442 |a Völkers, Mirko |m 133026442:Völkers, Mirko |d 910000 |d 910100 |e 910000PV133026442 |e 910100PV133026442 |k 0/910000/ |k 1/910000/910100/ |p 20 |y j | ||
| 998 | |g 1139390260 |a Doroudgar, Shirin |m 1139390260:Doroudgar, Shirin |d 50000 |e 50000PD1139390260 |k 0/50000/ |p 19 | ||
| 998 | |g 108916618 |a Katus, Hugo |m 108916618:Katus, Hugo |d 910000 |d 910100 |d 50000 |e 910000PK108916618 |e 910100PK108916618 |e 50000PK108916618 |k 0/910000/ |k 1/910000/910100/ |k 0/50000/ |p 18 | ||
| 998 | |g 141244976 |a Frey, Norbert |m 141244976:Frey, Norbert |d 910000 |d 910100 |e 910000PF141244976 |e 910100PF141244976 |k 0/910000/ |k 1/910000/910100/ |p 17 | ||
| 998 | |g 141244976 |a Frey, Norbert |m 141244976:Frey, Norbert |d 910000 |d 910100 |e 910000PF141244976 |e 910100PF141244976 |k 0/910000/ |k 1/910000/910100/ |p 17 | ||
| 998 | |g 130054844 |a Dieterich, Christoph |m 130054844:Dieterich, Christoph |d 910000 |d 910100 |e 910000PD130054844 |e 910100PD130054844 |k 0/910000/ |k 1/910000/910100/ |p 16 | ||
| 998 | |g 1194473482 |a Boileau, Etienne |m 1194473482:Boileau, Etienne |d 910000 |d 910100 |e 910000PB1194473482 |e 910100PB1194473482 |k 0/910000/ |k 1/910000/910100/ |p 15 | ||
| 998 | |g 1020115718 |a Sticht, Carsten |m 1020115718:Sticht, Carsten |d 60000 |d 60200 |d 60210 |e 60000PS1020115718 |e 60200PS1020115718 |e 60210PS1020115718 |k 0/60000/ |k 1/60000/60200/ |k 2/60000/60200/60210/ |p 14 | ||
| 998 | |g 12390708X |a Konstandin, Mathias |m 12390708X:Konstandin, Mathias |d 910000 |d 910100 |d 50000 |e 910000PK12390708X |e 910100PK12390708X |e 50000PK12390708X |k 0/910000/ |k 1/910000/910100/ |k 0/50000/ |p 13 | ||
| 998 | |g 1219456640 |a Furkel, Jennifer |m 1219456640:Furkel, Jennifer |d 910000 |d 911400 |e 910000PF1219456640 |e 911400PF1219456640 |k 0/910000/ |k 1/910000/911400/ |p 12 | ||
| 998 | |g 1293532800 |a Stroh, Claudia |m 1293532800:Stroh, Claudia |p 11 | ||
| 998 | |g 1252339836 |a Kamuf-Schenk, Verena |m 1252339836:Kamuf-Schenk, Verena |d 910000 |d 910100 |e 910000PK1252339836 |e 910100PK1252339836 |k 0/910000/ |k 1/910000/910100/ |p 10 | ||
| 998 | |g 1074309189 |a Jürgensen, Lonny |m 1074309189:Jürgensen, Lonny |d 910000 |d 910100 |e 910000PJ1074309189 |e 910100PJ1074309189 |k 0/910000/ |k 1/910000/910100/ |p 9 | ||
| 998 | |g 129353207X |a Ölschläger, Julie |m 129353207X:Ölschläger, Julie |d 50000 |e 50000PO129353207X |k 0/50000/ |p 8 | ||
| 998 | |g 1194474799 |a Kmietczyk, Vivien |m 1194474799:Kmietczyk, Vivien |d 910000 |d 910100 |e 910000PK1194474799 |e 910100PK1194474799 |k 0/910000/ |k 1/910000/910100/ |p 7 | ||
| 998 | |g 121922314X |a Varma, Eshita |m 121922314X:Varma, Eshita |d 910000 |d 910100 |e 910000PV121922314X |e 910100PV121922314X |k 0/910000/ |k 1/910000/910100/ |p 6 | ||
| 998 | |g 1181722845 |a Malovrh, Ellen |m 1181722845:Malovrh, Ellen |d 910000 |d 910100 |e 910000PM1181722845 |e 910100PM1181722845 |k 0/910000/ |k 1/910000/910100/ |p 5 | ||
| 998 | |g 1167970926 |a Sandmann, Christoph |m 1167970926:Sandmann, Christoph |d 50000 |e 50000PS1167970926 |k 0/50000/ |p 4 | ||
| 998 | |g 1192937465 |a Riechert, Eva |m 1192937465:Riechert, Eva |p 3 | ||
| 998 | |g 1194474667 |a Sandmann, Clara |m 1194474667:Sandmann, Clara |d 50000 |e 50000PS1194474667 |k 0/50000/ |p 2 | ||
| 998 | |g 1164508989 |a Górska, Aga |m 1164508989:Górska, Aga |d 910000 |d 910100 |e 910000PG1164508989 |e 910100PG1164508989 |k 0/910000/ |k 1/910000/910100/ |p 1 |x j | ||
| 999 | |a KXP-PPN1850820937 |e 434196318X | ||
| 999 | |a KXP-PPN1850820937 |e 4341962574 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"recId":"1850820937","id":{"doi":["10.15252/embr.202052170"],"eki":["1850820937"]},"name":{"displayForm":["Agnieszka A Górska, Clara Sandmann, Eva Riechert, Christoph Hofmann, Ellen Malovrh, Eshita Varma, Vivien Kmietczyk, Julie Ölschläger, Lonny Jürgensen, Verena Kamuf-Schenk, Claudia Stroh, Jennifer Furkel, Mathias H Konstandin, Carsten Sticht, Etienne Boileau, Christoph Dieterich, Norbert Frey, Hugo A Katus, Shirin Doroudgar & Mirko Völkers"]},"person":[{"family":"Górska","roleDisplay":"VerfasserIn","display":"Górska, Aga","given":"Aga","role":"aut"},{"role":"aut","roleDisplay":"VerfasserIn","given":"Clara","display":"Sandmann, Clara","family":"Sandmann"},{"role":"aut","family":"Riechert","given":"Eva","roleDisplay":"VerfasserIn","display":"Riechert, Eva"},{"role":"aut","roleDisplay":"VerfasserIn","given":"Christoph","display":"Sandmann, Christoph","family":"Sandmann"},{"given":"Ellen","roleDisplay":"VerfasserIn","display":"Malovrh, Ellen","family":"Malovrh","role":"aut"},{"role":"aut","family":"Varma","given":"Eshita","roleDisplay":"VerfasserIn","display":"Varma, Eshita"},{"display":"Kmietczyk, Vivien","roleDisplay":"VerfasserIn","given":"Vivien","family":"Kmietczyk","role":"aut"},{"role":"aut","family":"Ölschläger","roleDisplay":"VerfasserIn","display":"Ölschläger, Julie","given":"Julie"},{"family":"Jürgensen","roleDisplay":"VerfasserIn","display":"Jürgensen, Lonny","given":"Lonny","role":"aut"},{"role":"aut","display":"Kamuf-Schenk, Verena","roleDisplay":"VerfasserIn","given":"Verena","family":"Kamuf-Schenk"},{"role":"aut","family":"Stroh","roleDisplay":"VerfasserIn","given":"Claudia","display":"Stroh, Claudia"},{"given":"Jennifer","roleDisplay":"VerfasserIn","display":"Furkel, Jennifer","family":"Furkel","role":"aut"},{"family":"Konstandin","roleDisplay":"VerfasserIn","given":"Mathias","display":"Konstandin, Mathias","role":"aut"},{"display":"Sticht, Carsten","roleDisplay":"VerfasserIn","given":"Carsten","family":"Sticht","role":"aut"},{"role":"aut","display":"Boileau, Etienne","roleDisplay":"VerfasserIn","given":"Etienne","family":"Boileau"},{"family":"Dieterich","given":"Christoph","roleDisplay":"VerfasserIn","display":"Dieterich, Christoph","role":"aut"},{"role":"aut","family":"Frey","roleDisplay":"VerfasserIn","given":"Norbert","display":"Frey, Norbert"},{"given":"Hugo","roleDisplay":"VerfasserIn","display":"Katus, Hugo","family":"Katus","role":"aut"},{"family":"Doroudgar","roleDisplay":"VerfasserIn","display":"Doroudgar, Shirin","given":"Shirin","role":"aut"},{"role":"aut","roleDisplay":"VerfasserIn","display":"Völkers, Mirko","given":"Mirko","family":"Völkers"}],"type":{"bibl":"article-journal","media":"Online-Ressource"},"title":[{"title":"Muscle-specific Cand2 is translationally upregulated by mTORC1 and promotes adverse cardiac remodeling","title_sort":"Muscle-specific Cand2 is translationally upregulated by mTORC1 and promotes adverse cardiac remodeling"}],"origin":[{"dateIssuedDisp":"4 October 2021","dateIssuedKey":"2021"}],"relHost":[{"part":{"volume":"22","text":"22(2021), 12, Artikel-ID e52170, Seite 1-19","extent":"19","year":"2021","pages":"1-19","issue":"12"},"type":{"bibl":"periodical","media":"Online-Ressource"},"title":[{"title_sort":"EMBO reports","title":"EMBO reports"}],"recId":"320645622","id":{"zdb":["2025376-X"],"eki":["320645622"],"issn":["1469-3178"],"doi":["10.1002/(ISSN)1469-3178"]},"name":{"displayForm":["European Molecular Biology Organization"]},"pubHistory":["1.2000 -"],"physDesc":[{"extent":"Online-Ressource"}],"note":["Fortsetzung der Druck-Ausgabe","Gesehen am 11.03.25"],"language":["eng"],"disp":"European Molecular Biology OrganizationEMBO reports","corporate":[{"role":"aut","display":"European Molecular Biology Organization","roleDisplay":"VerfasserIn"}],"origin":[{"dateIssuedDisp":"[2000]-","publisher":"Nature Publishing Group UK ; EMBO Press ; Oxford Univ. Press ; Nature Publishing Group ; Wiley","publisherPlace":"[London] ; Heidelberg ; Oxford [u.a.] ; London [u.a.] ; Hoboken, NJ [u.a.]"}]}],"physDesc":[{"extent":"19 S."}],"note":["Gesehen am 22.06.2023"],"language":["eng"]} | ||
| SRT | |a GORSKAAGASMUSCLESPEC4202 | ||