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1 Movement Sciences, University of Illinois, Chicago, Chicago, IL, USA
* To whom correspondence should be addressed. E-mail: karyn.esser{at}uky.edu.
The purpose of this study was to identify the potential downstream functions associated with mTOR signaling during myotube hypertrophy. Terminally differentiated myotubes were serum stimulated for 3, 6, 12, 24 and 48 hr. This treatment resulted in significant myotube hypertrophy (protein/DNA) and increased RNA content (RNA/DNA) with no changes in DNA content or indices of cell proliferation. During myotube hypertrophy, the increase in RNA content was accompanied by an increase in Rb phosphorylation, and a corresponding increase in the availability of the rDNA transcription factor UBF. Serum stimulation also induced an increase in cyclin D1 protein expression in the differentiated myotubes with a concomitant increase in cyclin D1-dependent cdk-4 activity towards Rb. The increases in myotube hypertrophy and RNA content were blocked by rapamycin treatment, which also prevented the increase in cyclin D1 protein expression, cdk-4 activity, Rb phosphorylation, and the increase in UBF availability. Our findings demonstrate that activation of mTOR is necessary for myotube hypertrophy and suggest that the role of mTOR is, in part, to modulate cyclin D1-dependent cdk-4 activity in the regulation Rb and rRNA synthesis. Based on these results, we propose that common molecular mechanisms contribute to regulation of myotube hypertrophy and growth during the G1 phase of the cell cycle.
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