Mechanism of Action of Granaticin: Inhibition of Ribosomal RNA Maturation and Cell Cycle Specificity

1982 ◽  
Vol 71 (2) ◽  
pp. 197-200 ◽  
Author(s):  
Peter Heinstein
2005 ◽  
Vol 289 (6) ◽  
pp. C1457-C1465 ◽  
Author(s):  
Gustavo A. Nader ◽  
Thomas J. McLoughlin ◽  
Karyn A. Esser

The purpose of this study was to identify the potential downstream functions associated with mammalian target of rapamycin (mTOR) signaling during myotube hypertrophy. Terminally differentiated myotubes were serum stimulated for 3, 6, 12, 24, and 48 h. 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 tumor suppressor protein retinoblastoma (Rb) phosphorylation and a corresponding increase in the availability of the ribosomal DNA transcription factor upstream binding 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 cyclin-dependent kinase (CDK)-4 activity toward 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 of Rb and ribosomal RNA synthesis. On the basis of these results, we propose that common molecular mechanisms contribute to the regulation of myotube hypertrophy and growth during the G1 phase of the cell cycle.


Nature ◽  
1970 ◽  
Vol 227 (5257) ◽  
pp. 441-441
Author(s):  

1972 ◽  
Vol 1 (4) ◽  
pp. 219-228 ◽  
Author(s):  
Antonio Fantoni ◽  
Sandra Bordin ◽  
Mario Lunadei

2011 ◽  
Vol 10 (2) ◽  
pp. 242-254 ◽  
Author(s):  
Jeffrey J. Sutherland ◽  
Jonathan Low ◽  
Wayne Blosser ◽  
Michele Dowless ◽  
Thomas A. Engler ◽  
...  

2013 ◽  
Author(s):  
Jerome Mettetal ◽  
Derek Blair ◽  
Esha Gangoli ◽  
Patrick Vincent ◽  
Jeff Ecsedy ◽  
...  

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Irene Stefanini ◽  
Lisa Rizzetto ◽  
Damariz Rivero ◽  
Silvia Carbonell ◽  
Marta Gut ◽  
...  

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