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Live-cell decoding of labile post-translational modifications in APE1 with a rationally engineered nano-catcher
Ruilan Zhang1,2, Huaisyuan Xie1,2, Chenxu Zhu1,2
1Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
Nucleic Acids Research
|April 9, 2026
Summary
Researchers developed a nano-catcher to identify new protein modifications on human apurinic/apyrimidinic endonuclease 1 (APE1). This tool reveals how APE1 functions and offers potential cancer therapeutic targets.
Area of Science:
- Biochemistry
- Molecular Biology
- Nanotechnology
Background:
- Human apurinic/apyrimidinic endonuclease 1 (APE1) is crucial for DNA repair and redox regulation.
- Understanding APE1's post-translational modifications (PTMs) is vital but challenging.
- Existing methods struggle to capture dynamic PTMs in living cells.
Purpose of the Study:
- To develop a novel tool for capturing active APE1 with its labile PTMs in living cells.
- To identify previously unknown PTMs of APE1 and their locations.
- To investigate the functional impact of these PTMs on APE1 activity.
Main Methods:
- Engineered a biotin-regulated avidin-based nano-catcher (bMIPAPE1) using magnetic nanoparticles and polydopamine.
- Utilized surface-imprinted polymer technology for specific APE1 binding.
- Applied the nano-catcher in living cells to capture APE1 and its associated PTMs.
- Analyzed captured APE1 for novel post-translational modifications.
Main Results:
- Identified 25 novel PTMs on 18 different APE1 residues.
- Detected various modification types including acetylation, phosphorylation, and ubiquitination.
- Highlighted specific phosphorylation sites (Y264, Y269) and acetylation site (K63).
- Observed that several PTMs correlate with APE1 nuclear export.
- Demonstrated that bMIPAPE1 captures APE1 with high specificity and intracellular compatibility.
- Showed that bMIPAPE1 attenuates both DNA repair and redox functions of APE1.
Conclusions:
- The bMIPAPE1 nano-catcher is an effective tool for live-cell PTM profiling of APE1.
- This platform enables the discovery of novel PTMs and their functional consequences.
- Findings provide insights into APE1 regulation and suggest potential therapeutic strategies for cancer.
