Post-translational modifications and their implications in cancer

Abstract

Post-translational modifications (PTMs) are crucial regulatory mechanisms that alter the properties of a protein by covalently attaching a modified chemical group to some of its amino acid residues. PTMs modulate essential physiological processes such as signal transduction, metabolism, protein localization, and turnover and have clinical relevance in cancer and age-related pathologies. Majority of proteins undergo post-translational modifications, irrespective of their occurrence in or after protein biosynthesis. Post-translational modifications link to amino acid termini or side chains, causing the protein backbone to get cleaved, spliced, or cyclized, to name a few. These chemical modifications expand the diversity of the proteome and regulate protein activity, structure, locations, functions, and protein-protein interactions (PPIs). This ability to modify the physical and chemical properties and functions of proteins render PTMs vital. To date, over 200 different protein modifications have been reported, owing to advanced detection technologies. Some of these modifications include phosphorylation, glycosylation, methylation, acetylation, and ubiquitination. Here, we discuss about the existing as well as some novel post-translational protein modifications, with their implications in aberrant states, which will help us better understand the modified sites in different proteins and the effect of PTMs on protein functions in core biological processes and progression in cancer.

DAB2IP inhibits glucose uptake by modulating HIF-1α ubiquitination under hypoxia in breast cancer

“…Ubiquitylation is a crucial component of post-translational modifications that affects the function of target proteins during both healthy and pathological events [ 30 ]. In HIF-1α signaling, ubiquitylation plays an essential role in determining the half-life and transcriptional activity of HIF-1α, thus controlling the hypoxic response of mammalian cells [ 31 ].…”

A Tutorial Review of Labeling Methods in Mass Spectrometry-Based Quantitative Proteomics

“…145,146 Posttranslational modifications of proteins, such as phosphorylation, glycosylation, and ubiquitination, play a significant role in cancer progression. 147 Proteomics research focuses on these modifications to understand how they alter protein functions and signaling pathways in cancer cells, leading to uncontrolled growth and metastasis of cancer cells. 147 An important aspect of cancer proteomics is the identification of biomarkers.…”

“…147 Proteomics research focuses on these modifications to understand how they alter protein functions and signaling pathways in cancer cells, leading to uncontrolled growth and metastasis of cancer cells. 147 An important aspect of cancer proteomics is the identification of biomarkers. These biomarkers are proteins whose expression levels significantly change under carcinogenic conditions and can be used for early detection, prognosis, predicting treatment response, and monitoring disease progression.…”

“…Cancer cells exhibit abnormal protein expression patterns compared to normal cells . Proteomics techniques, such as MS and two-dimensional gel electrophoresis (2-DE), , are used to analyze these protein expressions to identify cancer-specific proteins (biomarkers) and explore the molecular mechanisms of tumor formation and development. , Post-translational modifications of proteins, such as phosphorylation, glycosylation, and ubiquitination, play a significant role in cancer progression . Proteomics research focuses on these modifications to understand how they alter protein functions and signaling pathways in cancer cells, leading to uncontrolled growth and metastasis of cancer cells …”

Cell Membrane Sialome: Sialic Acids as Therapeutic Targets and Regulators of Drug Resistance in Human Cancer Management

“…Cancers 2023, 15, 5103 2 of 24 the glycoconjugate landscape is dynamically formed by glycome-metabolic enzyme and glycome-metabolic pathway modifying factors that result in specific glycosylation patterns and their critical role in molecular and cellular biology. As a result of metabolic conversion, the activated monosaccharide units of dietary or molecular carbohydrate recycling origin are assembled into complex sugar chains in the Golgi apparatus and attached to the protein or lipid core via glycosyltransferases [2,3] (Figure 1). The sequential assembly of glycoproteins and glycolipids is orchestrated through essential collaboration between the endoplasmic reticulum (ER) and the Golgi apparatus.…”