Scripps VIVO scripps research logo

  • Index
  • Log in
  • Home
  • People
  • Organizations
  • Research
  • Events
Search form
As of April 1st VIVO Scientific Profiles will no longer updated for faculty, and the link to VIVO will be removed from the library website. Faculty profile pages will continue to be updated via Interfolio. VIVO will continue being used behind the scenes to update graduate student profiles. Please contact helplib@scripps.edu if you have questions.
How to download citations from VIVO | Alternative profile options

A chemoproteomic platform to quantitatively map targets of lipid-derived electrophiles

Academic Article
uri icon
  • Overview
  • Identity
  • Additional Document Info
  • View All
scroll to property group menus

Overview

related to degree

  • Blewett, Megan Marie, Ph.D. in Chemistry, Scripps Research , transferred from Harvard University 2012 - 2016

authors

  • Wang, C.
  • Weerapana, E.
  • Blewett, Megan Marie
  • Cravatt, Benjamin

publication date

  • January 2014

journal

  • Nature Methods  Journal

abstract

  • Cells produce electrophilic products with the potential to modify and affect the function of proteins. Chemoproteomic methods have provided a means to qualitatively inventory proteins targeted by endogenous electrophiles; however, ascertaining the potency and specificity of these reactions to identify the sites in the proteome that are most sensitive to electrophilic modification requires more quantitative methods. Here we describe a competitive activity-based profiling method for quantifying the reactivity of electrophilic compounds against >1,000 cysteines in parallel in the human proteome. Using this approach, we identified a select set of proteins that constitute 'hot spots' for modification by various lipid-derived electrophiles, including the oxidative stress product 4-hydroxy-2-nonenal (HNE). We show that one of these proteins, ZAK kinase, is labeled by HNE on a conserved, active site-proximal cysteine and that the resulting enzyme inhibition creates a negative feedback mechanism that can suppress the activation of JNK pathways normally induced by oxidative stress.

subject areas

  • Amino Acid Sequence
  • Breast Neoplasms
  • Catalytic Domain
  • Cell Line, Tumor
  • Cysteine
  • Dose-Response Relationship, Drug
  • Electrochemistry
  • Female
  • Gene Expression Regulation, Neoplastic
  • HEK293 Cells
  • Humans
  • Inhibitory Concentration 50
  • Lipids
  • Mass Spectrometry
  • Molecular Sequence Data
  • Oxidative Stress
  • Prostaglandin D2
  • Protein Kinases
  • Protein Processing, Post-Translational
  • Proteome
  • Proteomics
  • Sequence Homology, Amino Acid
scroll to property group menus

Identity

PubMed Central ID

  • PMC3901407

International Standard Serial Number (ISSN)

  • 1548-7091

Digital Object Identifier (DOI)

  • 10.1038/nmeth.2759

PubMed ID

  • 24292485
scroll to property group menus

Additional Document Info

start page

  • 79

end page

  • 85

volume

  • 11

issue

  • 1

©2022 The Scripps Research Institute | Terms of Use | Powered by VIVO

  • About
  • Contact Us
  • Support