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Depletion of mammalian target of rapamycin (mTOR) via siRNA mediated knockdown leads to stabilization of β ‐catenin and elicits distinct features of cardiomyocyte hypertrophy
Author(s) -
Hagenmueller Marco,
Malekar Pratima,
Fieger Christiane,
Weiss Celine S.,
Buss Sebastian J.,
Wolf David,
Katus Hugo A.,
Hardt Stefan E.
Publication year - 2010
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2009.10.080
Subject(s) - pi3k/akt/mtor pathway , gene knockdown , microbiology and biotechnology , gsk 3 , rptor , cardiac myocyte , myocyte , cell growth , protein kinase b , beta catenin , catenin , biology , chemistry , kinase , signal transduction , wnt signaling pathway , gene , biochemistry
Cardiac myocyte growth is under differential control of mammalian target of rapamycin (mTOR) and glycogen‐synthase‐kinase‐3 β (GSK3 β ). Whereas active GSK3 β 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 GSK3 β protein in cardiac myocytes. As a result, GSK3 β 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 GSK3 β activities, indicating that GSK3 β ‐dependent stabilization of β ‐catenin in cardiac myocytes is influenced by mTOR.