Imperial College London

ProfessorMichaelSchneider

Faculty of MedicineNational Heart & Lung Institute

Chair in Cardiology
 
 
 
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Contact

 

+44 (0)013 34621727m.d.schneider Website

 
 
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Location

 

ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Abdellatif:1998:10.1128/mcb.18.11.6729,
author = {Abdellatif, M and Packer, SE and Michael, LH and Zhang, D and Charng, MJ and Schneider, MD},
doi = {10.1128/mcb.18.11.6729},
journal = {Mol Cell Biol},
pages = {6729--6736},
title = {A Ras-dependent pathway regulates RNA polymerase II phosphorylation in cardiac myocytes: implications for cardiac hypertrophy.},
url = {http://dx.doi.org/10.1128/mcb.18.11.6729},
volume = {18},
year = {1998}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - Despite extensive evidence implicating Ras in cardiac muscle hypertrophy, the mechanisms involved are unclear. We previously reported that Ras, through an effector-like function of Ras GTPase-activating protein (GAP) in neonatal cardiac myocytes (M. Abdellatif et al., J. Biol. Chem. 269:15423-15426, 1994; M. Abdellatif and M. D. Schneider, J. Biol. Chem. 272:527-533, 1997), can up-regulate expression from a comprehensive set of promoters, including both cardiac cell-specific and constitutive ones. To investigate the mechanism(s) underlying these earlier findings, we have used recombinant adenoviruses harboring a dominant negative Ras (17N Ras) allele or the N-terminal domain of GAP (nGAP), responsible for the Ras-like effector function. Inhibition of endogenous Ras reduced basal levels of [3H]uridine and [3H]phenylalanine incorporation into total RNA, mRNA, and protein, with parallel changes in apparent cell size. In addition, 17N Ras markedly inhibited phosphorylation of the C-terminal domain (CTD) of RNA polymerase II (pol II), known to regulate transcript elongation, accompanied by down-regulation of its principal kinase, cyclin-dependent kinase 7 (Cdk7). In contrast, nGAP elicited the opposite effects on each of these parameters. Furthermore, cotransfection of constitutively active Ras (12R Ras) with wild-type pol II, rather than a truncated mutant lacking the CTD, demonstrated that Ras activation of transcription was dependent on the pol II CTD. Consistent with a potential role for this pathway in the development of cardiac myocyte hypertrophy, alpha1-adrenergic stimulation similarly enhanced pol II phosphorylation and Cdk7 expression, where both effects were inhibited by dominant negative Ras, while pressure overload hypertrophy led to an increase in both hyperphosphorylated and hypophosphorylated pol II in addition to Cdk7.
AU - Abdellatif,M
AU - Packer,SE
AU - Michael,LH
AU - Zhang,D
AU - Charng,MJ
AU - Schneider,MD
DO - 10.1128/mcb.18.11.6729
EP - 6736
PY - 1998///
SN - 0270-7306
SP - 6729
TI - A Ras-dependent pathway regulates RNA polymerase II phosphorylation in cardiac myocytes: implications for cardiac hypertrophy.
T2 - Mol Cell Biol
UR - http://dx.doi.org/10.1128/mcb.18.11.6729
UR - https://www.ncbi.nlm.nih.gov/pubmed/9774686
VL - 18
ER -