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      Transcription Factors in Heart: Promising Therapeutic Targets in Cardiac Hypertrophy

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          Abstract

          Regulation of gene expression is central to cell growth, differentiation and diseases. Context specific and signal dependent regulation of gene expression is achieved to a large part by transcription factors. Cardiac transcription factors regulate heart development and are also involved in stress regulation of the adult heart, which may lead to cardiac hypertrophy. Hypertrophy of cardiac myocytes is an outcome of the imbalance between prohypertrophic factors and anti-hypertrophic factors. This is initially a compensatory mechanism but sustained hypertrophy may lead to heart failure. The growing knowledge of transcriptional control mechanisms is helpful in the development of novel therapies. This review summarizes the role of cardiac transcription factors in cardiac hypertrophy, emphasizing their potential as attractive therapeutic targets to prevent the onset of heart failure and sudden death as they can be converging targets for current therapy.

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          Most cited references120

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          FoxOs at the crossroads of cellular metabolism, differentiation, and transformation.

          Forkhead transcription factors of the FoxO subfamily are emerging as a shared component among pathways regulating diverse cellular functions, such as differentiation, metabolism, proliferation, and survival. Their transcriptional output is controlled via a two-tiered mechanism of phosphorylation and acetylation. Modest alterations of this balance can result in profound effects. The gamut of phenotypes runs from protection against diabetes and predisposition to neoplasia, conferred by FoxO loss of function, to increased cellular survival and a marked catabolic response associated with gain of function.
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            HES and HERP families: multiple effectors of the Notch signaling pathway.

            Notch signaling dictates cell fate and critically influences cell proliferation, differentiation, and apoptosis in metazoans. Multiple factors at each step-ligands, receptors, signal transducers and effectors-play critical roles in executing the pleiotropic effects of Notch signaling. Ligand-binding results in proteolytic cleavage of Notch receptors to release the signal-transducing Notch intracellular domain (NICD). NICD migrates into the nucleus and associates with the nuclear proteins of the RBP-Jkappa family (also known as CSL or CBF1/Su(H)/Lag-1). RBP-Jkappa, when complexed with NICD, acts as a transcriptional activator, and the RBP-Jkappa-NICD complex activates expression of primary target genes of Notch signaling such as the HES and enhancer of split [E(spl)] families. HES/E(spl) is a basic helix-loop-helix (bHLH) type of transcriptional repressor, and suppresses expression of downstream target genes such as tissue-specific transcriptional activators. Thus, HES/E(spl) directly affects cell fate decisions as a primary Notch effector. HES/E(spl) had been the only known effector of Notch signaling until a recent discovery of a related but distinct bHLH protein family, termed HERP (HES-related repressor protein, also called Hey/Hesr/HRT/CHF/gridlock). In this review, we summarize the recent data supporting the idea of HERP being a new Notch effector, and provide an overview of the similarities and differences between HES and HERP in their biochemical properties as well as their tissue distribution. One key observation derived from identification of HERP is that HES and HERP form a heterodimer and cooperate for transcriptional repression. The identification of the HERP family as a Notch effector that cooperates with HES/E(spl) family has opened a new avenue to our understanding of the Notch signaling pathway. Copyright 2003 Wiley-Liss, Inc.
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              MyoD and the transcriptional control of myogenesis.

              The basic helix-loop-helix myogenic regulatory factors MyoD, Myf5, myogenin and MRF4 have critical roles in skeletal muscle development. Together with the Mef2 proteins and E proteins, these transcription factors are responsible for coordinating muscle-specific gene expression in the developing embryo. This review highlights recent studies regarding the molecular mechanisms by which the muscle-specific myogenic bHLH proteins interact with other regulatory factors to coordinate gene expression in a controlled and ordered manner.
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                Author and article information

                Journal
                Curr Cardiol Rev
                Curr Cardiol Rev
                CCR
                Current Cardiology Reviews
                Bentham Science Publishers
                1573-403X
                1875-6557
                November 2011
                November 2011
                : 7
                : 4
                : 262-271
                Affiliations
                Department of Biotechnology, Jaypee Institute of Information Technology, NOIDA 201307, India
                Author notes
                [* ] Address correspondence to this author at the Department of Biotechnology, Jaypee Institute of Information Technology University, Noida 210307, India; Tel: + (91)-120-2594210; Fax: + (91)-120-2400986; E-mail: vibha.rani@ 123456jiit.ac.in
                Article
                CCR-7-262
                10.2174/157340311799960618
                3322445
                22758628
                be114eac-49aa-4c3f-a4f1-f7bf56a2871f
                © 2011 Bentham Science Publishers

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.5/), which permits unrestrictive use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 12 May 2011
                : 8 January 2012
                : 8 January 2011
                Categories
                Article

                Cardiovascular Medicine
                therapeutic targets,cardiac hypertrophy,cardiac transcription factors,pro-hypertrophic,anti-hypertrophic,heart failure.

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