ArticleCell discovery2023
A microprotein N1DARP encoded by LINC00261 promotes Notch1 intracellular domain (N1ICD) degradation via disrupting USP10-N1ICD interaction to inhibit chemoresistance in Notch1-hyperactivated pancreatic cancer.
Article in Cell discovery, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 41 citations in OpenAlex.
- Deubiquitination of NICD1 by USP10 Restrains Esophageal Cancer: A Link Between NOTCH1 Stabilization, Oxidative Stress, and Ferroptosis.Neoplasia (New York, N.Y.) · 2026Article
- CPT1A through succinylation regulates the CTCF/LINC01503‒91aa feedback loop to promote gemcitabine resistance in pancreatic ductal adenocarcinoma.Clinical and translational medicine · 2026Article
- Targeting the Notch signaling pathway in digestive system cancers: from bench to bedside.Cancer cell international · 2026Review
- Comprehensive annotation and analysis of human microproteins by human microprotein atlas platform.Communications chemistry · 2026Article
- USP10 deubiquitinase: Physiological function, diseases and therapeutic target (Review).International journal of molecular medicine · 2026Review
- Pathological and therapeutic implications of Notch overexpression in claudin-low breast cancers.Human cell · 2026Article
- Microproteins in Human Physiology and Pathology.Biochemistry · 2026Review
- MYC-induced USP10 stabilizes SOX4 to promote thymocyte proliferation and leukemia onset in mice.Nature communications · 2026Article
- Review
- USP10 regulates HIF2α stability by deubiquitinating HIF2α regardless ofTranslational andrology and urology · 2026Article
- USP10 promotes cell proliferation and gemcitabine resistance in pancreatic cancer by the regulation of IGF2BP3-STEAP3.Oncogene · 2026Article
- The dual role of the Notch signaling pathway in digestive system cancers.European journal of medical research · 2026Review
- Co-targeting MRPS7-23 synergistically enhances cisplatin efficacy to suppress nasopharyngeal carcinoma growth and metastasis.International journal of biological sciences · 2026Article
- The association between periodontal disease and pancreatic cancer: epidemiology, mechanisms, and implications for clinical management.Frontiers in cellular and infection microbiology · 2026Review
- USP10 stabilizes FOXM1 through KAT5-mediated acetylation to suppress cell senescence and promote melanoma malignant progression.International journal of biological sciences · 2026Article
- Post-Translational Modifications: Key "Regulators" of Pancreatic Cancer Malignant Phenotype-Advances in Mechanisms and Targeted Therapies.Biomedicines · 2025Review
- CD276-directed supramolecular nanoplatform with pH-triggered gemcitabine release for potent tumor stromal and vascular suppression.International journal of pharmaceutics: X · 2025Article
- The multifaceted roles of deubiquitinating enzymes (DUBs) in pancreatic ductal adenocarcinoma.Cell death & disease · 2025Review
- Abnormal mitochondrial structure and function in brown adipose tissue of SLC35A4-MP knockout mice.Science advances · 2025Article
- Increasing linc00261 expression may predict well cancer prognosis, based on the meta-analysis.Discover oncology · 2025Review
Corrections and comments
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Authors and funding
17 authors at 2 institutions in 1 country.
Funding
Abstract
The extensively activated Notch signaling pathway in pancreatic cancer cells is important in carcinogenesis, chemoresistance, and recurrence. Targeting this pathway is a promising therapeutic strategy for pancreatic cancer; however, few successful approaches have been reported, and currently used molecular inhibitors of this pathway exhibit limited clinical benefits. In this study, we identified a previously uncharacterized microprotein, Notch1 degradation-associated regulatory polypeptide (N1DARP), encoded by LINC00261. N1DARP knockout accelerated tumor progression and enhanced stem cell properties in pancreatic cancer organoids and LSL-Kras, LSL-Trp53, and Pdx1-Cre (KPC) mice. Mechanistically, N1DARP suppressed canonical and non-canonical Notch1 pathways by competitively disrupting the interaction between N1ICD and ubiquitin-specific peptidase 10 (USP10), thereby promoting K11- and K48-linked polyubiquitination of N1ICD. To evaluate the therapeutic potential of N1DARP, we designed a cell-penetrating stapled peptide, SAH-mAH2-5, with a helical structure similar to that of N1DARP that confers remarkable physicochemical stability. SAH-mAH2-5 interacted with and promoted the proteasome-mediated degradation of N1ICD. SAH-mAH2-5 injection provided substantial therapeutic benefits with limited off-target and systemic adverse effects in Notch1-activated pancreatic cancer models. Taken together, these findings confirm that N1DARP acts as a tumor suppressor and chemosensitizer by regulating USP10-Notch1 oncogenic signaling, and suggest a promising therapeutic strategy targeting the N1DARP-N1ICD interaction in Notch1-activated pancreatic cancer.
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Registered trials
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 OpenQuestion graph.