Evolutionary, structural and functional features of cellular signalling networks
type: CreativeWork
description: The post-translational modification of proteins is a fundamental means of biological information processing, with important functions in development, homeostasis and disease. Post-translational modifications (PTMs) can dynamically diversify the proteome in response to intracellular and extracellular signals. Since thousands of modified residues as well as entirely new modification types have recently been discovered in proteins, elucidating their biological functions and identifying the protein components of these PTM systems is a fundamental problem. Chapter 1 gives an overview of the types and known biological functions of different PTMs, as well as experimental methods used to detect them. Intrinsic disorder in proteins is introduced as a structural feature which may influence local evolutionary rates. Several examples of complex PTM signalling systems are then described. Chapter 2 presents a study of the evolution of modified amino acids in human proteins. By analysing sequence, polymorphism and mutation data at the species, population and individual levels, we observed significant evolutionary constraints on all PTM types for which extensive data was available, as well as overrepresentation of amino acids which mimic modified residues at equivalent positions. Chapter 3 applies a framework for the identification of important components of PTM signalling systems to lysine acetylation. The proteins of this system were found to be similarly conserved as essential genes. Their evolutionary histories suggested a conserved origin in chromatin regulation, followed by functional diversification. Chapter 4 extends the scope to signalling via transcriptional regulation, and presents a comprehensive overview of the interactome of the stem cell transcription factor Oct4. The results presented here facilitated characterisation of a novel post-translational modifier of Oct4, the glycosyltransferase Ogt. Chapter 5 highlights my key findings from applying evolutionary and data …
abstract: The post-translational modification of proteins is a fundamental means of biological information processing, with important functions in development, homeostasis and disease. Post-translational modifications (PTMs) can dynamically diversify the proteome in response to intracellular and extracellular signals. Since thousands of modified residues as well as entirely new modification types have recently been discovered in proteins, elucidating their biological functions and identifying the protein components of these PTM systems is a fundamental problem. Chapter 1 gives an overview of the types and known biological functions of different PTMs, as well as experimental methods used to detect them. Intrinsic disorder in proteins is introduced as a structural feature which may influence local evolutionary rates. Several examples of complex PTM signalling systems are then described. Chapter 2 presents a study of the evolution of modified amino acids in human proteins. By analysing sequence, polymorphism and mutation data at the species, population and individual levels, we observed significant evolutionary constraints on all PTM types for which extensive data was available, as well as overrepresentation of amino acids which mimic modified residues at equivalent positions. Chapter 3 applies a framework for the identification of important components of PTM signalling systems to lysine acetylation. The proteins of this system were found to be similarly conserved as essential genes. Their evolutionary histories suggested a conserved origin in chromatin regulation, followed by functional diversification. Chapter 4 extends the scope to signalling via transcriptional regulation, and presents a comprehensive overview of the interactome of the stem cell transcription factor Oct4. The results presented here facilitated characterisation of a novel post-translational modifier of Oct4, the glycosyltransferase Ogt. Chapter 5 highlights my key findings from applying evolutionary and data …
author: Lang, Benjamin
language: en
keywords: Systems Biology, Cell Signalling, Cell Signaling, Networks, Evolution, Post-translational modifications, Posttranslational modifications, Post translational modifications, PTMs, PTM, Phosphorylation, Acetylation, Methylation, Glycosylation, N-linked glycosylation, Intrinsically disordered proteins, Intrinsic disorder, Unstructured proteins, Non-globular proteins, Nonglobular proteins, Evolutionary rates, Variation, Human variation, Human disease, Oct4, Stem cells, Interactome, Lysine acetylation, K-ac, K-me, R-me, S-p, T-p, Y-p, Modified amino acids, Data integration, Computational Biology, Evolutionary pressure, Sequence conservation, Sequence evolution, Conservation, Evolutionary conservation, Ogt, Glycosyltransferase
license: https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/a5078ced-b01f-42a6-aadf-5dbbdcfe0f6a/download
license: https://creativecommons.org/licenses/by-nc-sa/4.0/
date published: 2013-07-20
date modified: 2026-07-22T22:24:07Z
provider: Cambridge University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Cambridge

PropertyValue
property ID: DOI
value: 10.17863/CAM.39120