ArticleCell death and differentiation2019
Regulating BRCA1 protein stability by cathepsin S-mediated ubiquitin degradation.
Article in Cell death and differentiation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 46 citations in OpenAlex.
- Pemetrexed increases BRCA1 protein stability and sensitizes TNBC cells to radiotherapy.Oncology reports · 2026Article
- Silencing SGO2 by Oxamic Acid Dissociates Glycolysis and BRCA1-Mediated DNA Repair to Improve the Chemosensitivity of Lung Adenocarcinoma.Exploration (Beijing, China) · 2026Article
- Cathepsin B Nuclear Flux in a DNA-Guided "Antinuclear Missile" Cancer Therapy.ACS central science · 2024Article
- SOSTDC1 Nuclear Translocation Facilitates BTIC Maintenance and CHD1-Mediated HR Repair to Promote Tumor Progression and Olaparib Resistance in TNBC.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- A high-throughput approach to identify BRCA1-downregulating compounds to enhance PARP inhibitor sensitivity.iScience · 2024Article
- Radiosensitizing effect of a novel CTSS inhibitor by enhancing BRCA1 protein stability in triple-negative breast cancer cells.Cancer science · 2024Article
- The deubiquitinating enzyme USP4 regulates BRCA1 stability and function.NPJ breast cancer · 2024Article
- Cysteine Cathepsins in Breast Cancer: Promising Targets for Fluorescence-Guided Surgery.Molecular imaging and biology · 2023Review
- Genome stability‑related lncRNA ZFPM2‑AS1 promotes tumor progression via miR‑3065‑5p/XRCC4 in hepatocellular carcinoma.International journal of oncology · 2023Article
- Functional Analyses of Rare Germline MissenseGenes · 2023Article
- MEOX2-mediated regulation of Cathepsin S promotes cell proliferation and motility in glioma.Cell death & disease · 2022Article
- Cathepsin K activity controls cachexia-induced muscle atrophy via the modulation of IRS1 ubiquitination.Journal of cachexia, sarcopenia and muscle · 2022Article
- BBIT20 inhibits homologous DNA repair with disruption of the BRCA1-BARD1 interaction in breast and ovarian cancer.British journal of pharmacology · 2021Article
- Exploiting DNA Damage Repair in Precision Cancer Therapy: BRCA1 as a Prime Therapeutic Target.Cancers · 2021Review
- Modulation of Cathepsin S (Animals : an open access journal from MDPI · 2021Article
- LEDGF/p75 Is Required for an Efficient DNA Damage Response.International journal of molecular sciences · 2021Article
- SIRT2 promotes BRCA1-BARD1 heterodimerization through deacetylation.Cell reports · 2021Article
- Cathepsin S Cleaves BAX as a Novel and Therapeutically Important Regulatory Mechanism for Apoptosis.Pharmaceutics · 2021Article
- The Role of Cysteine Peptidases in Hematopoietic Stem Cell Differentiation and Modulation of Immune System Function.Frontiers in immunology · 2021Review
- Decursin inhibits cell growth and autophagic flux in gastric cancer via suppression of cathepsin C.American journal of cancer research · 2021Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cathepsin S (CTSS) is a cysteine protease that is thought to play a role in many physiological and pathological processes including tumor growth, angiogenesis, and metastasis; it has been identified as a radiation response gene. Here, we examined the role of CTSS in regulating the DNA damage response in breast cancer cells. Activating CTSS (producing the cleavage form of the protein) by radiation induced proteolytic degradation of BRCA1, which ultimately suppressed DNA double-strand break repair activity. Depletion of CTSS by RNAi or expression of a mutant type of CTSS enhanced the protein stability of BRCA1 by inhibiting its ubiquitination. CTSS interacted with the BRCT domain of BRCA1 and facilitated ubiquitin-mediated proteolytic degradation of BRCA1, which was tightly associated with decreased BRCA1-mediated DNA repair activity. Treatment with a pharmacological CTSS inhibitor inhibited proteolytic degradation of BRCA1 and restored BRCA1 function. Depletion of CTSS by shRNA delayed tumor growth in a xenograft mouse model, only in the presence of functional BRCA1. Spontaneously uced rat mammary tumors and human breast cancer tissues with high levels of CTSS expression showed low BRCA1 expression. From these data, we suggest that CTSS inhibition is a good strategy for functional restoration of BRCA1 in breast cancers with reduced BRCA1 protein stability.
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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 OpenQuestion graph.