Regulation of rDNA transcription during endothelin-1-induced hypertrophy of neonatal cardiomyocytes. Hyperphosphorylation of upstream binding factor, an rDNA transcription factor

Circulation Research
J LuykenL Rothblum

Abstract

Treatment of cultured neonatal cardiomyocytes with endothelin-1 and phorbol 12-myristate 13-acetate (PMA) results in cardiomyocyte hypertrophy. However, the signal transduction pathways involved in this process are poorly understood. Because increased ribosome biogenesis is a requisite for hypertrophy, we sought to (1) confirm the hypothesis that these two hypertrophic agents did indeed induce rRNA synthesis and (2) examine the mechanism through which this induction was accomplished. In this study, hypertrophy of contraction-arrested neonatal cardiomyocytes induced by treatment with either endothelin-1 or PMA was associated with increased rDNA transcription. Western blots demonstrated that the enhanced rates of rDNA transcription were not mediated by increased amounts of either RNA polymerase I or upstream binding factor (UBF), an rDNA transcription factor. However, immunoprecipitation of [32P] orthophosphate-labeled UBF from hypertrophying neonatal cardiomyocytes suggested that the increased rate of rDNA transcription may be due to the hyperphosphorylation of UBF, which would increase the activity of UBF. The increase in UBF phosphorylation occurred within 3 to 6 hours after exposure to either agent, was maximal at 12 hours, a...Continue Reading

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Citations

Jun 8, 2002·Biochemical and Biophysical Research Communications·Zheng-ping XuGuo-fu Hu
Jul 25, 2003·Journal of Molecular and Cellular Cardiology·Peter H Sugden
Aug 2, 2003·Clinical and Experimental Pharmacology & Physiology·R D HannanY Brandenburger
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Nov 17, 2012·Biochimica Et Biophysica Acta·K M HannanR B Pearson
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Oct 16, 2001·Nucleic Acids Research·I Hirschler-LaszkiewiczL I Rothblum
Aug 19, 2014·ACS Applied Materials & Interfaces·Alexandre J S RibeiroBeth L Pruitt
Jul 30, 2004·The EMBO Journal·Gretchen PoortingaRoss D Hannan
Mar 17, 2006·The EMBO Journal·Sarah J GoodfellowRobert J White
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Sep 3, 2009·Pharmacology & Therapeutics·Rebecca H RitchieBarbara K Kemp-Harper

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