Depletion of mammalian target of rapamycin (mTOR) via siRNA mediated knockdown leads to stabilization of beta-catenin and elicits distinct features of cardiomyocyte hypertrophy

作者：Hagenmueller Marco^*; Malekar Pratima; Fieger Christiane; Weiss Celine S; Buss Sebastian J; Wolf David; Katus Hugo A; Hardt Stefan E

来源：FEBS LETTERS, 2010, 584(1): 74-80.

DOI：10.1016/j.febslet.2009.10.080

• siRNA
• mTOR
• Wnt signaling
• Cardiac hypertrophy

Cardiac myocyte growth is under differential control of mammalian target of rapamycin (mTOR) and glycogen-synthase-kinase-3 beta (GSK3 beta). Whereas active GSK3 beta 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 beta protein in cardiac myocytes. As a result, GSK3 beta target protein beta-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 beta activities, indicating that GSK3 beta-dependent stabilization of beta-catenin in cardiac myocytes is influenced by mTOR.

• 出版日期2010-1-4