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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
12
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pubmed:dateCreated |
2009-6-22
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pubmed:abstractText |
Emerging evidence illustrates the importance of the positive transcription elongation factor (P-TEF)b in control of global RNA synthesis, which constitutes a major feature of the compensatory response to diverse hypertrophic stimuli in cardiomyocytes. P-TEFb complex, composed of cyclin T and cdk9, is critical for elongation of nascent RNA chains via phosphorylation of the carboxyl-terminal domain of RNA polymerase (Pol) II. We and others have shown that the activity of P-TEFb is inhibited by its association with cardiac lineage protein (CLP)-1, the mouse homolog of human HEXIM1, in various physiological and pathological conditions. To investigate the mechanism of control of P-TEFb activity by CLP-1 in cardiac hypertrophy, we used a transgenic mouse model of hypertrophy caused by overexpression of calcineurin in the heart. We observed that the level of CLP-1 associated with P-TEFb was reduced markedly in hypertrophic hearts. We also generated bigenic mice (MHC-cyclin T1/CLP-1(+/-)) by crossing MHC-cyclin T1 transgenic mice with CLP-1 heterozygote. The bigenic mice exhibit enhanced susceptibility to hypertrophy that is accompanied with an increase in cdk9 activity via an increase in serine 2 phosphorylation of carboxyl-terminal domain and an increase in GLUT1/GLUT4 ratio. These mice have compensated systolic function without evidence of fibrosis and reduced lifespan. These data suggest that the reduced level of CLP-1 introduced in the background of elevated levels of cyclin T1 elevates derepression of P-TEFb activity and emphasizes the importance of the role of CLP-1 in the mechanism governing compensatory hypertrophy in cardiomyocytes.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/19443839-10086361,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19443839-10377279,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19443839-10415515,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19443839-10448907,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19443839-10606624,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19443839-10617616,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19443839-10775485,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19443839-10845093,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19443839-10958691,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19443839-11248077,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19443839-11248078,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19443839-11299243,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19443839-11395543,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19443839-11909516,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19443839-12119119,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19443839-12368904,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19443839-12379584,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19443839-12388248,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19443839-12695656,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19443839-12832472,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19443839-12893779,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19443839-12900219,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19443839-14580347,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19443839-14766360,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19443839-15172687,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19443839-15272022,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19443839-15276474,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19443839-15286705,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19443839-15297879,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19443839-16822720,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19443839-16936699,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19443839-16959964,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19443839-17459355,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19443839-17956865,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19443839-19542017,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19443839-7675081,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19443839-8576950,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19443839-9568714,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19443839-9774686
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Ccnt1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin T,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase 9,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclins,
http://linkedlifedata.com/resource/pubmed/chemical/Glucose Transporter Type 1,
http://linkedlifedata.com/resource/pubmed/chemical/Glucose Transporter Type 4,
http://linkedlifedata.com/resource/pubmed/chemical/Hexim1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/RNA,
http://linkedlifedata.com/resource/pubmed/chemical/RNA Polymerase II,
http://linkedlifedata.com/resource/pubmed/chemical/Slc2a1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Slc2a4 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
1524-4571
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
19
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pubmed:volume |
104
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1347-54
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pubmed:dateRevised |
2011-6-1
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pubmed:meshHeading |
pubmed-meshheading:19443839-Humans,
pubmed-meshheading:19443839-Animals,
pubmed-meshheading:19443839-Mice,
pubmed-meshheading:19443839-Male,
pubmed-meshheading:19443839-RNA,
pubmed-meshheading:19443839-Disease Models, Animal,
pubmed-meshheading:19443839-Crosses, Genetic,
pubmed-meshheading:19443839-Myocytes, Cardiac,
pubmed-meshheading:19443839-RNA Polymerase II,
pubmed-meshheading:19443839-Cardiomyopathy, Dilated,
pubmed-meshheading:19443839-Transcription Factors,
pubmed-meshheading:19443839-Mice, Knockout,
pubmed-meshheading:19443839-Cyclins,
pubmed-meshheading:19443839-Glucose Transporter Type 4,
pubmed-meshheading:19443839-Glucose Transporter Type 1
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