Proteomics and Protein Post-Translational Modification

Special Issue Editors


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Guest Editor
Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, One Gustave Levy Place, New York, NY 10029, USA
Interests: heart failure; protein-protein interaction; post-translational modifications; gene therapy; small molecule therapy

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Guest Editor
Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Interests: cardiac gene therapy; heart failure; translational research; large animal experiment; cardiac physiology; LV unloading
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Special Issue Information

Dear Colleagues,

JCDD is launching a Special Issue on "Proteomics and Protein Post-Translational Modification in Heart Disease". Post-translational modifications (PTMs) have been shown to alter protein function by creating new protein binding sites, abrogating protein–protein interactions, or inducing allosteric regulation. Furthermore, the rapid and transient nature of many PTMs allow efficient signal transmission in response to internal and environmental stimuli. PTMs are predominantly triggered by enzymes, and the enzymes responsible are thus attractive targets for therapeutic interventions. Modifications can be grouped according to their stability or transience (reversible versus irreversible): Irreversible types (such as irreversible redox modifications or protein deamidation) are often associated with aging or tissue injury, whereas transient modifications are associated with signal propagation and regulation. This is particularly important in the setting of heart disease, which comprises a diverse range of acute (such as ischemia/reperfusion), chronic (such as heart failure, dilated cardiomyopathy) and genetic (such as hypertrophic cardiomyopathy) disease states, all of which have been associated with protein PTM. This field is rapidly evolving, using multiple approaches, including but not restricted to computational biology, protein arrays, and biochemical analyses, proteomic mapping, molecular and transgenic techniques both in vivo and in vitro. This interesting combination of applications allows for new interpretations and analyses for understanding the evolutionary, developmental and functional therapeutic potential in the setting of heart disease.

Dr. Chang Won Kho
Dr. Kiyotake Ishikawa
Guest Editors

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Keywords

  • Heart disease
  • Heart failure
  • Protein–protein interaction
  • Post-translational modifications
  • Proteomics
  • Gene therapy

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Published Papers (1 paper)

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Article
Strategy for Identification of Phosphorylation Levels of Low Abundance Proteins in Vivo for Which Antibodies Are not Available
by Kozo Hayashi, Ryo Yamashita, Ritsuko Takami, Toshikatsu Matsui, Masamitsu Gotou, Tomoyuki Nishimoto and Hiroyuki Kobayashi
J. Cardiovasc. Dev. Dis. 2017, 4(4), 17; https://doi.org/10.3390/jcdd4040017 - 8 Oct 2017
Viewed by 4979
Abstract
Protein function is mainly modulated by dynamic reversible or irreversible post-translational modifications. Among them, the identification of protein phosphorylation sites and changes in phosphorylation levels in vivo are of considerable interest for a better understanding of the protein function. Thus, effective strategies for [...] Read more.
Protein function is mainly modulated by dynamic reversible or irreversible post-translational modifications. Among them, the identification of protein phosphorylation sites and changes in phosphorylation levels in vivo are of considerable interest for a better understanding of the protein function. Thus, effective strategies for the quantitative determination of phosphorylation degrees for low abundant proteins, for which antibodies are not available, are required in order to evaluate the functional regulation of proteins attributed to phosphorylation. In this study, we used the heart β1-adrenergic receptor (Adrb1) as a model protein and developed FLAG-Adrb1 knock-in mice, in which the FLAG tag was inserted at the N-terminus of Adrb1. The phosphorylation sites and levels of Adrb1 in the heart were elucidated by immuno-affinity purification followed by quantitative mass spectrometry analysis using ion intensity ratio of the phosphorylated peptide versus corresponding unphosphorylated peptide. The phosphorylation levels at Ser274 and Ser462 of Adrb1 were approximately 0.25 and 0.0023. This effective strategy should be useful for not only analyzing site-specific phosphorylation levels of target proteins, but also quantifying the expression levels of proteins of interest when appropriate antibodies are not available. Full article
(This article belongs to the Special Issue Proteomics and Protein Post-Translational Modification)
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