Cell surface thermal proteome profiling tracks perturbations and drug targets on the plasma membrane

Kalxdorf, Mathias; Günthner, Ina; Becher, Isabelle; Kurzawa, Nils; Knecht, Sascha; Savitski, Mikhail M.; Eberl, H. Christian; Bantscheff, Marcus

doi:10.1038/s41592-020-01022-1

Cited by 69 publications

(57 citation statements)

References 58 publications

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“…Large-scale molecular techniques such as genomics, transcriptomics, proteomics, and metabonomics have been applied to obtain deep and comprehensive understanding of biological systems. Membrane-associated proteins accomplish numerous functions in cell recognition, signal transportation which are involved in the pathogenesis of many human diseases [3,4]. The identi cation of speci c plasma membrane proteins was expected to use as imaging marker and therapeutic target for cancers.…”

Section: Introductionmentioning

confidence: 99%

WITHDRAWN: Integrative Analysis of the Proteome and Transcriptome in Gastric Cancer Identified Membrane Protein LRP1B as a Potential Biomarker

Miao

Yang

Wen

et al. 2022

Preprint

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Background: Membrane proteins participate in cell recognition and malignant transformation, and have value in terms of tumor detection and therapy. The aim of this study was to discover unique membrane proteins for gastric cancer (GC) with proteomic analysis of cell lines.Methods: Using the data-independent acquisition (DIA) strategy, we compared the relative expression levels of membrane proteins between GC and noncancer cells. Promising candidates were identified by matching proteomic data to The Cancer Genome Atlas (TCGA) GC transcriptional profiles, and then accessed their expression using immunohistochemistry.Results: Based on about 4700 membrane proteins quantified, 2774 differentially expressed membrane proteins were identified between GC and normal cell lines. Molecular function analysis indicated that these abnormally expressed proteins were mainly involved in biological metabolic processes. Conjoint analysis of transcriptomes and proteomes provided 11 potential biomarkers (GPRC5A, PSAT1, NUDCD1, RCC2, IPO4, FAM91A1, KANK2, PRADC1, NME4, METTL7A and LRP1B) for further exploration. The downregulation of LRP1B in GC was validated by immunohistochemistry on 66 matched pairs of normal and GC tissues.Conclusions: These data provide a comprehensive overview of the proteomic phenotypes of membrane proteins in GC tumorigenesis. Based on the integrative analysis, LRP1B was identified as a meaningful indicator assisting in GC diagnosis and molecular detection.

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Section: Introductionmentioning

confidence: 99%

WITHDRAWN: Integrative Analysis of the Proteome and Transcriptome in Gastric Cancer Identified Membrane Protein LRP1B as a Potential Biomarker

Miao

Yang

Wen

et al. 2022

Preprint

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“…In addition, target identification does not result from direct observation of an interaction, but is inferred from a higher protein melting temperature. Furthermore, identification of membrane [70] or low‐abundant proteins remains challenging. In contrast to above methods, the development of clickable or biotinylated probes requires often challenging chemical synthesis.…”

Section: Discussionmentioning

confidence: 99%

Probes for Photoaffinity Labelling of Kinases

et al. 2021

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Protein kinases, one of the largest enzyme superfamilies, regulate many physiological and pathological processes. They are drug targets for multiple human diseases, including various cancer types. Probes for the photoaffinity labelling of kinases are important research tools for the study of members of this enzyme superfamily. In this review, we discuss the design principles of these probes, which are mainly derived from inhibitors targeting the ATP pocket. Overall, insights from crystal structures guide the placement of photoreactive groups and detection tags. This has resulted in a wide variety of probes, of which we provide a comprehensive overview. We also discuss several areas of application of these probes, including the identification of targets and off‐targets of kinase inhibitors, mapping of their binding sites, the development of inhibitor screening assays, the imaging of kinases, and identification of protein binding partners.

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“…the identification of phenyl hydroxylase as an off-target of the HDAC inhibitor panobinostat [105]. Further optimized workflows have described the successful application to transmembrane targets [106][107][108] and even to in vivo models and patient material [109]. Several approaches use differences in susceptibility to limited proteolysis upon compound treatment to identify proteome-wide compound interaction, including DARTS [110] and LiP-MS [111].…”

Section: Protein Stability-based Chemoproteomic Approachesmentioning

confidence: 99%

Proteomics in the pharmaceutical and biotechnology industry: a look to the next decade

Lill¹,

Mathews²,

Rose³

et al. 2021

Expert Review of Proteomics

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Introduction: Pioneering technologies such as proteomics have helped fuel the biotechnology and pharmaceutical industry with the discovery of novel targets and an intricate understanding of the activity of therapeutics and their various activities in vitro and in vivo. The field of proteomics is undergoing an inflection point, where new sensitive technologies are allowing intricate biological pathways to be better understood, and novel biochemical tools are pivoting us into a new era of chemical proteomics and biomarker discovery. In this review, we describe these areas of innovation, and discuss where the fields are headed in terms of fueling biotechnological and pharmacological research and discuss current gaps in the proteomic technology landscape. Areas Covered: Single cell sequencing and single molecule sequencing. Chemoproteomics. Biological matrices and clinical samples including biomarkers. Computational tools including instrument control software, data analysis. Expert Opinion: Proteomics will likely remain a key technology in the coming decade, but will have to evolve with respect to type and granularity of data, cost and throughput of data generation as well as integration with other technologies to fulfill its promise in drug discovery.

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Cell surface thermal proteome profiling tracks perturbations and drug targets on the plasma membrane

Cited by 69 publications

References 58 publications

WITHDRAWN: Integrative Analysis of the Proteome and Transcriptome in Gastric Cancer Identified Membrane Protein LRP1B as a Potential Biomarker

WITHDRAWN: Integrative Analysis of the Proteome and Transcriptome in Gastric Cancer Identified Membrane Protein LRP1B as a Potential Biomarker

Probes for Photoaffinity Labelling of Kinases

Proteomics in the pharmaceutical and biotechnology industry: a look to the next decade

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