ArticleEMBO reports2022
Dipeptidyl peptidase 9 triggers BRCA2 degradation and promotes DNA damage repair.
Article in EMBO reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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Who cites it
18 citing papers in PubMed, 28 citations in OpenAlex.
- Proximity labeling reveals non-catalytic interactions between DPP9 and ubiquitin signaling complexes.Cellular and molecular life sciences : CMLS · 2026Article
- Reduced DPP9 levels sensitize experimental breast tumors to combinatory treatment with irradiation and Olaparib.Frontiers in oncology · 2026Article
- A Photocaged N-Phosphonopiperidinone as a Selective Photo-Cleavable DPP8/9 Inhibitor.Chembiochem : a European journal of chemical biology · 2025Article
- PARP inhibitor-induced anti-tumour chemokine response is suppressed by dipeptidyl peptidase 4 (DPP4) in ovarian cancer.British journal of cancer · 2025Article
- A fluorescent sensor for real-time monitoring of DPP8/9 reveals crucial roles in immunity and cancer.Life science alliance · 2025Article
- DPP8/9 processing of human AK2 unmasks an IAP binding motif.EMBO reports · 2025Article
- The multifunctional regulatory post-proline protease dipeptidyl peptidase 9 and its inhibitors: new opportunities for therapeutics.Cellular and molecular life sciences : CMLS · 2025Review
- Sulphostin-inspired N-phosphonopiperidones as selective covalent DPP8 and DPP9 inhibitors.Nature communications · 2025Article
- The serine protease DPP9 and the redox sensor KEAP1 form a mutually inhibitory complex.The Journal of biological chemistry · 2025Article
- DPP9 regulates NQO1 and ROS to promote resistance to chemotherapy in liver cancer cells.Redox biology · 2024Article
- Dipeptidyl peptidases and E3 ligases of N-degron pathways cooperate to regulate protein stability.The Journal of cell biology · 2024Article
- Dipeptidyl-Aminopeptidases 8 and 9 Regulate Autophagy and Tamoxifen Response in Breast Cancer Cells.Cells · 2023Article
- Article
- DPP8/9 are not Required to Cleave Most Proline-Containing Peptides.Israel journal of chemistry · 2023Article
- Chemoproteomics-Enabled Identification of 4-Oxo-β-Lactams as Inhibitors of Dipeptidyl Peptidases 8 and 9.Angewandte Chemie (International ed. in English) · 2022Article
- Dipeptidyl peptidase 9 triggers BRCA2 degradation and promotes DNA damage repair.EMBO reports · 2022Article
- New insights into the role of dipeptidyl peptidase 8 and dipeptidyl peptidase 9 and their inhibitors.Frontiers in pharmacology · 2022Review
- Article
Corrections and comments
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Authors and funding
18 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
N-terminal sequences are important sites for post-translational modifications that alter protein localization, activity, and stability. Dipeptidyl peptidase 9 (DPP9) is a serine aminopeptidase with the rare ability to cleave off N-terminal dipeptides with imino acid proline in the second position. Here, we identify the tumor-suppressor BRCA2 as a DPP9 substrate and show this interaction to be induced by DNA damage. We present crystallographic structures documenting intracrystalline enzymatic activity of DPP9, with the N-terminal Met1-Pro2 of a BRCA21-40 peptide captured in its active site. Intriguingly, DPP9-depleted cells are hypersensitive to genotoxic agents and are impaired in the repair of DNA double-strand breaks by homologous recombination. Mechanistically, DPP9 targets BRCA2 for degradation and promotes the formation of RAD51 foci, the downstream function of BRCA2. N-terminal truncation mutants of BRCA2 that mimic a DPP9 product phenocopy reduced BRCA2 stability and rescue RAD51 foci formation in DPP9-deficient cells. Taken together, we present DPP9 as a regulator of BRCA2 stability and propose that by fine-tuning the cellular concentrations of BRCA2, DPP9 alters the BRCA2 interactome, providing a possible explanation for DPP9's role in cancer.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.