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Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

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Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
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A Mass Spectrometry-Based Approach to Identify Phosphoprotein Phosphatases and their Interactors
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Small molecules that target phosphorylation dependent protein-protein interaction.

Nobumoto Watanabe1, Hiroyuki Osada2

  • 1Bio-Active Compounds Discovery Research Unit, RIKEN Center for Sustainable Resource Science, Wako, Saitama 351-0198, Japan; Bio-Probe Research Group, RIKEN-Max Planck Joint Research Center for Systems Chemical Biology, Wako, Saitama 351-0198, Japan.

Bioorganic & Medicinal Chemistry
|March 28, 2016
PubMed
Summary

Small molecules targeting phosphorylation-dependent protein interactions offer cancer treatment potential. This review highlights modulators for 14-3-3, Plk1 polo box, and SCF ubiquitin ligase F-box proteins.

Keywords:
Protein phosphorylationProtein–protein interactionSmall molecule

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Area of Science:

  • Molecular Biology
  • Biochemistry
  • Pharmacology

Background:

  • Protein-protein interactions are crucial for signal transduction pathways.
  • Phosphorylation frequently mediates these interactions, altering protein function.
  • Dysregulated signaling contributes to diseases like cancer.

Purpose of the Study:

  • To review small molecules that modulate phosphorylation-dependent protein-protein interactions.
  • To focus on three key interaction modules: 14-3-3, Plk1 polo box domain, and F-box proteins.
  • To introduce a novel screening system for identifying such modulators.

Main Methods:

  • Literature review of small molecules targeting specific protein-protein interaction modules.
  • Description of an original high-throughput screening system.
  • Analysis of the role of these modules in disease pathogenesis.

Main Results:

  • Identification and summary of existing small molecules that modulate 14-3-3, Plk1 polo box, and F-box protein interactions.
  • Demonstration of the utility of the developed screening system for discovering novel modulators.
  • Emphasis on the therapeutic potential of these small molecules.

Conclusions:

  • Small molecules targeting phosphorylation-dependent protein interactions are promising therapeutic agents.
  • The reviewed modules (14-3-3, Plk1 polo box, F-box) are critical nodes in signaling pathways.
  • The developed screening system provides a valuable tool for future drug discovery in oncology and other diseases.