Jump to main content
Jump to site search
Access to RSC content Close the message box

Continue to access RSC content when you are not at your institution. Follow our step-by-step guide.


Issue 7, 2011
Previous Article Next Article

Relating protein adduction to gene expression changes: a systems approach

Author affiliations

Abstract

Modification of proteins by reactive electrophiles such as the 4-hydroxy-2-nonenal (HNE) plays a critical role in oxidant-associated human diseases. However, little is known about protein adduction and the mechanism by which protein damage elicits adaptive effects and toxicity. We developed a systems approach for relating protein adduction to gene expression changes through the integration of protein adduction, gene expression, protein–DNA interaction, and proteinprotein interaction data. Using a random walk strategy, we expanded a list of responsive transcription factors inferred from gene expression studies to upstream signaling networks, which in turn allowed overlaying protein adduction data on the network for the prediction of stress sensors and their associated regulatory mechanisms. We demonstrated the general applicability of transcription factor-based signaling network inference using 103 known pathways. Applying our workflow on gene expression and protein adduction data from HNE-treatment not only rediscovered known mechanisms of electrophile stress but also generated novel hypotheses regarding protein damage sensors. Although developed for analyzing protein adduction data, the framework can be easily adapted for phosphoproteomics and other types of protein modification data.

Graphical abstract: Relating protein adduction to gene expression changes: a systems approach

Back to tab navigation

Supplementary files

Article information


Submitted
12 Jan 2011
Accepted
21 Apr 2011
First published
19 May 2011

Mol. BioSyst., 2011,7, 2118-2127
Article type
Paper

Relating protein adduction to gene expression changes: a systems approach

B. Zhang, Z. Shi, D. T. Duncan, N. Prodduturi, L. J. Marnett and D. C. Liebler, Mol. BioSyst., 2011, 7, 2118
DOI: 10.1039/C1MB05014A

Search articles by author

Spotlight

Advertisements