Quantitative approaches to probe the acetylproteome
Name
859883403-MIT.pdf
Description
Full printable version
Size
28.91 MB
Format
Adobe PDF
Checksum (MD5)
ba595360584e2c22d9ef284b2aec6856
Author(s)
Bryson, Bryan David
Advisor(s)
Forest M. White.
Date Issued
2013
Publisher
Massachusetts Institute of Technology
Abstract
Lysine acetylation is a prevalent post-translational modification whose multi-varied biological roles have recently emerged. While having all the necessary components of a signaling network, lysine acetylation studies have been limited to a small subset of proteins and pathways. Using a quantitative unbiased mass spectrometry approach, we explored the role of growth factor stimulation on lysine acetylation. Although the growth factors bind receptor tyrosine kinases, growth factor stimulation resulted in rapid and dynamic changes in lysine acetylation. Furthermore, we demonstrated that short-term HDAC inhibition alters phosphotyrosine-signaling networks. To better understand this behavior, a suite of biochemical and computational methods were developed. Bromodomains were engineered to explore binding preferences using degenerate peptide arrays as well as develop acetyllysine affinity reagents as an alternative to anti-acetyllysine antibodies. Additionally, bioorthogonal proteomics were employed to identify acetyltransferase substrates. Taken together, the knowledge generated and the methods developed provide a toolkit for the analysis of lysine acetylation networks in the context of many biological processes as well as diseases.
Description
Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biological Engineering, 2013.
Cataloged from PDF version of thesis.
Includes bibliographical references (p. 173-175).
Subjects
Biological Engineering.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
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