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APE1 (apurinic/apyrimidinic endonuclease 1): newly identified post-translational modifications (PTMs)

ABSTRACT: APE1 (apurinic/apyrimidinic endonuclease 1) is a multifunctional protein essential for both DNA base excision repair and redox signaling. However, its post-translational modifications (PTMs), which are key to modulating its cellular functions, remain largely uncharacterized due to their dynamic and labile nature. In this study, we developed a novel biotin-regulated avidin-based magnetic nanoparticle platform (bMIPAPE1) that selectively captures active APE1 from living cells under native conditions. This approach preserves labile PTMs and enables downstream mass spectrometry-based proteomic analysis. Using this tool, we identified 27 previously unreported PTMs at 18 distinct residues, including modifications with critical functional implications, such as phosphorylation at Y269 and dual acetylation/palmitoylation at K228. Furthermore, we uncovered PTMs associated with subcellular localization, including modifications at K203, C208, and K63 that correlated with APE1 nuclear export. Beyond enrichment and profiling, bMIPAPE1 also inhibits the enzymatic functions of APE1 in cells, offering potential therapeutic relevance. This project showcases an innovative method for real-time PTM profiling of endogenous proteins in complex cellular environments, with implications for cancer biology and targeted drug discovery.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Meiping Zhao

LAB HEAD: Meiping Zhao

PROVIDER: PXD067266 | Pride | 2026-03-17

REPOSITORIES: Pride

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			Action	DRS
	23157_ZRL0607_APE1_M1P.raw	Raw
	23157_ZRL0607_APE1_M1P_ModifiedPeptides.xlsx	Xlsx
	23157_ZRL0607_APE1_M1P_peptides.xlsx	Xlsx
	23157_ZRL0607_APE1_M1P_proteins.xlsx	Xlsx
	23157_ZRL_APE1_M1P.mzTab	Mztab

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