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Forest M. White. Bryson, Bryan David Massachusetts Institute of Technology. Department of Biological Engineering. Massachusetts Institute of Technology. Department of Biological Engineering 2013-10-24T17:41:15Z 2013-10-24T17:41:15Z 2013 2013 http://hdl.handle.net/1721.1/81664 859883403 Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biological Engineering, 2013. Cataloged from PDF version of thesis. Includes bibliographical references (p. 173-175). 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. by Bryan David Bryson. Ph.D. 175 p. eng Massachusetts Institute of Technology MIT theses are protected by copyright. They may be viewed, downloaded, or printed from this source but further reproduction or distribution in any format is prohibited without written permission. http://dspace.mit.edu/handle/1721.1/7582 Biological Engineering. Quantitative approaches to probe the acetylproteome Thesis application/pdf false Publication unknown unknown <Publication xmlns="https://www.openaire.eu/cerif-profile/1.1/" id="faf63faa-46e1-43e3-9a2f-e02ef7daaedb"> <Type xmlns="https://www.openaire.eu/cerif-profile/vocab/COAR_Publication_Types">http://purl.org/coar/resource_type/c_1843</Type> <Language>eng</Language> <Title>Quantitative approaches to probe the acetylproteome</Title> <PublishedIn> <Publication> </Publication> </PublishedIn> <PublicationDate>2013</PublicationDate> <Authors> <Author> <DisplayName>Bryson, Bryan David</DisplayName> <Affiliation> <OrgUnit> </OrgUnit> </Affiliation> </Author> </Authors> <Editors> </Editors> <Publishers> <Publisher> <DisplayName>Massachusetts Institute of Technology</DisplayName> <OrgUnit /> </Publisher> </Publishers> <License>http://dspace.mit.edu/handle/1721.1/7582</License> <Keyword>Biological Engineering.</Keyword> <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.</Abstract> <Access xmlns="http://purl.org/coar/access_right" > </Access> </Publication>