Depletion of mammalian target of rapamycin (mTOR) via siRNA mediated knockdown leads to stabilization of β-catenin and elicits distinct features of cardiomyocyte hypertrophy
Cardiac myocyte growth is under differential control of mammalian target of rapamycin (mTOR) and glycogen-synthase-kinase-3β (GSK3β). Whereas active GSK3β negatively regulates growth and down-regulates cellular protein synthesis, activation of the mTOR pathway promotes protein expression and cell gr...
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| Main Authors: | , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
2010
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| In: |
FEBS letters
Year: 2010, Volume: 584, Issue: 1, Pages: 74-80 |
| ISSN: | 1873-3468 |
| DOI: | 10.1016/j.febslet.2009.10.080 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.febslet.2009.10.080 Verlag, lizenzpflichtig, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1016/j.febslet.2009.10.080 
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| Author Notes: | Marco Hagenmueller, Pratima Malekar, Christiane Fieger, Celine S. Weiss, Sebastian J. Buss, David Wolf, Hugo A. Katus, Stefan E. Hardt |
| Summary: | Cardiac myocyte growth is under differential control of mammalian target of rapamycin (mTOR) and glycogen-synthase-kinase-3β (GSK3β). Whereas active GSK3β negatively regulates growth and down-regulates cellular protein synthesis, activation of the mTOR pathway promotes protein expression and cell growth. Here we report that depletion of mTOR via siRNA mediated knockdown causes marked down-regulation of GSK3β protein in cardiac myocytes. As a result, GSK3β target protein β-catenin becomes stabilized and translocates into the nucleus. Moreover, mTOR knockdown leads to increase in cardiac myocyte surface area and produces an up-regulation of the fetal gene program. Our findings suggest a new type of convergence of mTOR and GSK3β activities, indicating that GSK3β-dependent stabilization of β-catenin in cardiac myocytes is influenced by mTOR. |
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| Item Description: | Available online 31 October 2009 Gesehen am 15.06.2023 |
| Physical Description: | Online Resource |
| ISSN: | 1873-3468 |
| DOI: | 10.1016/j.febslet.2009.10.080 |