Pharmacological targeting of CDK9 in cardiac hypertrophy

0359307 - ÚEB 2012 RIV US eng J - Journal Article
Kryštof, Vladimír - Chamrád, Ivo - Jorda, Radek - Kohoutek, J.
Pharmacological targeting of CDK9 in cardiac hypertrophy.
Medicinal Research Reviews. Roč. 30, č. 4 (2010), s. 646-666. ISSN 0198-6325. E-ISSN 1098-1128
R&D Projects: GA ČR GA204/08/0511; GA ČR GA301/09/1832; GA ČR GA301/08/1649
Institutional research plan: CEZ:AV0Z50380511
Keywords : P-TEFb * cardiac myocyte * cardiac hypertrophy
Subject RIV: CE - Biochemistry
Impact factor: 10.228, year: 2010

Cardiac hypertrophy allows the heart to adapt to workload, but persistent or unphysiological stimulus can result in pump failure. Cardiac hypertrophy is characterized by an increase in the size of differentiated cardiac myocytes. At the molecular level, growth of cells is linked to intensive transcription and translation. Several cyclin-dependent kinases (CDKs) have been identified as principal regulators of transcription, and among these CDK9 is directly associated with cardiac hypertrophy. CDK9 phosphorylates the C-terminal domain of RNA polymerase II and thus stimulates the elongation phase of transcription. Chronic activation of CDK9 causes not only cardiac myocyte enlargement but also confers predisposition to heart failure. Due to the long interest of molecular oncologists and medicinal chemists in CDKs as potential targets of anticancer drugs, a portfolio of small-molecule inhibitors of CDK9 is available.
Permanent Link: http://hdl.handle.net/11104/0197111