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Drugs of Abuse and Addiction
Published in Sahab Uddin, Rashid Mamunur, Advances in Neuropharmacology, 2020
Shalini Mani, Chahat Kubba, Aarushi Singh
There are multiple myocyte enhancing factor-2 (MEF2) proteins which get expressed in nucleus accumbens of brain and these proteins form homo or heterodimers to regulate gene transcription (Pulipparacharuvil, 2008; Robison and Nestler, 2012). Cocaine administration suppresses MEF2 protein activity through some novel mechanisms involving cAMP. Increased dendritic spine density induced by cocaine is also a result of this decreased activity of MEF2 proteins. Still a lot is to be known about the MEF2 activity in other drugs of abuse (Pulipparacharuvil, 2008; Chen, 2010).
The Role of Epigenetics in Skeletal Muscle Adaptations to Exercise and Exercise Training
Published in Peter M. Tiidus, Rebecca E. K. MacPherson, Paul J. LeBlanc, Andrea R. Josse, The Routledge Handbook on Biochemistry of Exercise, 2020
The mechanisms controlling post-translational modification of histones revolve around the enzymes that regulate these particular processes. These include histone acetyltransferases and histone deacetylases, which add and remove acetylation, respectively, histone methyltransferases, demethylases, kinases, and phosphatases (48). Each family of enzymes has a number of isoforms with different substrate specificities, mechanism of activation, and regulation of sub-cellular localization, which are controlled by different intracellular signalling pathways. This ensures that only specific regions of DNA become accessible to transcriptional regulators upon activation of defined signalling pathways. These same signalling mechanisms often also regulate sequence-specific transcription factors and coactivators to provide precise control over the transcriptional response. For example, myocyte enhancer factor 2 (MEF2) transcription is acetylated by the p300 histone acetyltransferase, leading to enhanced MEF2 transcriptional activity (37). Therefore, p300 simultaneously acetylates histones and a DNA-binding transcription factor to enhance gene transcription. Adding complexity to the regulatory system are histone variants, which differ in sequence from the canonical histone proteins, but incorporate into nucleosomes regularly throughout larger chromatin fibres (17). These variants can create nucleosomes with distinct structural and regulatory features. For example, Cse4/CENP-A, a histone 3 variant, lacks a number of phosphorylation and acetylation sites that are associated with transcriptional activation (3). It is thought that the CENP-A variant retains a nucleosome in its compacted and transcriptionally repressed state (3).
MiR-33a-5p targets NOMO1 to modulate human cardiomyocyte progenitor cells proliferation and differentiation and apoptosis
Published in Journal of Receptors and Signal Transduction, 2021
Wang Xing, Tiangang Li, Yixuan Wang, Yi Qiang, Chencheng Ai, Hanbo Tang
Transcription factor GATA4 has become a the nuclear effector of several cardiac signaling pathways that regulate critical cardiac cascades through post-translational modifications and protein-protein interactions [30], and deletion of GATA4 from mesodermal progenitors during early development would lead to absence of cardiomyocytes [31]. Troponin T (TnT), the tropomyosin-binding and thin filament anchoring subunit, of the troponin complex in regulating of muscle contraction [32]. Cardiac troponin T (cTnT) is considered to be a reliable biomarker of myocardial injury in humans [33]. And during the differentiation process of cardiomyocytes, cTnT expression was increased [34]. Myocyte enhancer factor2C (MEF2C) is a member of the MEF2 family, functions as a key role in activating cardiac-specific embryonic genes expressions [35]. It was worth noting that expressions of GATA4, cTnT and MEF2C were down-regulated by up-regualtion of miR-33a-5p in the present study, indicating that degree of hCMPCs differentiation into cardiomyocytes was inhibited by up-regulation of miR-33a-5p.
Chaperone-mediated autophagy as a therapeutic target for Parkinson disease
Published in Expert Opinion on Therapeutic Targets, 2018
Philip Campbell, Huw Morris, Anthony Schapira
The transcription factor myocyte enhancer factor 2 (MEF2), which has four isoforms (MEF2A-D) was first described as a transcription factor involved in muscle cell differentiation [53]. It has been subsequently shown that MEF2s are highly expressed in brain and play a role in neuronal differentiation and survival [54,55]. It is now known that one isoform of MEF (MEF2D) is regulated, at least in part, by CMA with inhibition of CMA leading to an accumulation of cytoplasmic MEF2D [37]. Although this would intuitively suggest that a reduction in CMA would beneficial, it has been shown that the accumulated cytosolic MEF2D has reduced DNA binding and is therefore less functional. This suggests CMA preferentially removes nonfunctional MEF2D and that accumulation of the non-functional form compromises the action of active MEF2D [37]. The same study went on to show that both mutant (A53T) and WT ɑ-synuclein disrupted MEF2D binding to hsc70, leading to MEF2D accumulation and cell death. Such toxicity could be attenuated by maintaining nuclear MEF2D levels by modification of MEF2D to impede its export from the nucleus [37]. These results therefore provide a link to how accumulation of WT ɑ-synuclein may exert its toxic effects as well as the potential role of MEF2D in PD pathogenesis. In support of this Yang et al. went on to show that MEF2D levels were increased in both the brains of ɑ-synuclein transgenic mice and PD patients, suggesting MEF2D-ɑ-synuclein interactions may be important in vivo [37].
Post-translational quantitation by SRM/MRM: applications in cardiology
Published in Expert Review of Proteomics, 2018
Erica Gianazza, Cristina Banfi
Even before the studies reported above, Cox et al. evaluated the phosphorylation levels of myocyte enhancer factor 2A (MEF2A) using MRM MS in a mammalian cell line [98]. This study is not focused on a specific CVD, but it is well known that MEF2, a transcriptional regulator, whose activity is controlled by phosphorylation, is involved in the development of cardiac and skeletal muscle cells. Moreover, it regulates stress response during cardiac hypertrophy and tissue remodeling. The phosphorylation of this protein causes an increase or reduction of its activity based on the type of modified amino acids. Despite this study focusing on mammalian MEF2A, the authors wanted to demonstrate that targeted MRM information-dependent acquisition (IDA) successfully identifies low fmol levels of phosphopeptides and it is a powerful technique for the future quantitation of phosphorylated proteins also in the human complex biological matrix.