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Analysis of Confounding Factors in Reactive Cysteine Profiling Reveals Enhanced Chromatin-Protein Association via CDK7 Inhibition by THZ1
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DOI：10.1021/acschembio.6c00101.png)
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Abstract
En 中文
Recent advances in activity-based proteome profiling (ABPP) have enabled the global mapping of cysteine ligandability, uncovering novel biological insights and opportunities for identifying disease vulnerabilities. While both live-cell-based and native-lysate-based ABPP have been applied, how cysteine ligandability differs between these systems and what factors influence these measurements remain unclear. Building on our previous development of a high-throughput TMT-ABPP workflow for native lysates, here we adapt the protocol for live cells and systematically compare cysteine ligandability across both platforms. Our analysis reveals three major contributors to the discrepancies: in-cellular cysteine accessibility, protein abundance changes, and protein relocalization. Notably, we highlight that the CDK7 inhibitor THZ1 induces substantial protein relocalization and promotes chromatin binding. Together, these results provide a practical framework for ABPP experimental design and data interpretation, supporting the more accurate application of ABPP in functional proteomics and drug discovery.
Keywords:
Mass spectrometry
Monomers
Peptides and proteins
Proteomics
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