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| Status |
Public on Jul 30, 2021 |
| Title |
Cand2 links pathological mTORC1 signaling to adverse cardiac remodeling by regulating Grk5 expression |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
The mechanistic target of rapamycin (mTOR) is a key regulator of 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 largely unknown. A cardiomyocyte genome-wide sequencing approach was used to define mTOR-dependent post-transcriptional gene expression control at the level of mRNA translation. This approach identified 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 found 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 for adverse pathological cardiac remodeling.
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| |
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| Overall design |
Comparision of WT mice vs global Cand2 KO mice
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| |
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| Contributor(s) |
Völkers M |
| Citation(s) |
34605609 |
| Submission date |
Jun 26, 2020 |
| Last update date |
Nov 02, 2021 |
| Contact name |
Carsten Sticht |
| Organization name |
University Heidelberg
|
| Department |
ZMF
|
| Street address |
Theodor-Kutzer-Ufer
|
| City |
Mannheim |
| ZIP/Postal code |
68169 |
| Country |
Germany |
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| Platforms (1) |
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| Samples (10)
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| Relations |
| BioProject |
PRJNA642148 |
| SRA |
SRP268929 |
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