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Deciphering Endogenous SUMO-1 Landscape: A Novel Peptide Ligand Approach

ABSTRACT: Protein SUMOylation orchestrates diverse cellular processes and is linked to diseases such as cancer and neurodegenerative disorders. However, large-scale identification endogenous SUMO-1 poses challenges due to current enrichment methods limitations and its lower abundance compared to SUMO-2/3. To solve this problem, we developed a series of novel peptide ligands via phage display, specifically targeting the C-terminal region of SUMO-1 remnants. These peptide ligands exhibited robust affinity for SUMO-1 modified peptide segments, facilitating the development of a peptide-based enrichment strategy. Using this strategy, we mapped 1312 SUMOylation sites in HeLa cells, unveiling a comprehensive SUMOylation landscape. We further applied our approach to the Alzheimer's disease (AD) model mice, revealing 1364 SUMOylation sites and 991 endogenous SUMOylation proteins in mice brain tissues. Notably, AD mice brain tissues exhibited significantly elevated SUMO-1 modification levels. Differential protein analysis, including previously unreported SUMOylation substrates, were identified and the reliability of our identification strategy was validated through SUMO-1 modification of ULK2 in AD mice brain tissues by co-immunoprecipitation. This work advances endogenous SUMO-1 proteome, providing insights and potential disease targets, particularly for AD. Moreover, our strategy, bolstered by the utility of phage display technology, opens new avenues for the development of enrichment materials in various other post-translational modifications.

ORGANISM(S): Homo Sapiens

SUBMITTER: Lihua Zhang

PROVIDER: PXD050705 | iProX | Mon Mar 18 00:00:00 GMT 2024

REPOSITORIES: iProX

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