ArticleThe Journal of cell biology2013
BRCA1 loss activates cathepsin L-mediated degradation of 53BP1 in breast cancer cells.
Article in The Journal of cell biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 81 citations in OpenAlex.
- Multifaceted Role of Vitamin D in Breast Cancer: A Systematic Review of Genetic and Pathway-Based Mechanisms.Asian Pacific journal of cancer prevention : APJCP · 2024Pooled it
- Trial
- Nuclear cathepsin L induces DNA damage by regulating DNA repair factors in ovarian cancer.Oncogene · 2026Article
- The Potential Role of Vitamin D inInternational journal of molecular sciences · 2026Review
- Cathepsin L as a Driver of Tumour Invasion and a Novel Therapeutic Target in Ovarian Cancer.Cancers · 2026Review
- Metabolic drivers of genome instability in cancer: mechanisms and therapeutic opportunities.Experimental hematology & oncology · 2026Review
- Integration of Single-cell and Bulk Transcriptome Analyses Unravels a Macrophage-based Gene Signature for Prognostication and Treatment in Triple-negative Breast Cancer.International journal of medical sciences · 2026Article
- A cancer persistent DNA repair circuit driven by MDM2, MDM4 (MDMX), and mutant p53 for recruitment of MDC1 and 53BP1 on chromatin.Nucleic acids research · 2025Article
- Hypoxia increases methylated histones to prevent histone clipping and heterochromatin redistribution during Raf-induced senescence.Nucleic acids research · 2025Article
- Review
- Histone Tail Cleavage as a Mechanism for Epigenetic Regulation.International journal of molecular sciences · 2024Review
- Cathepsin K-Activated Probe for Fluoro-Photoacoustic Imaging of Early Osteolytic Metastasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Vitamin D and Calcium Supplement Use and High-Risk Breast Cancer: A Case-Control Study amongCancers · 2023Article
- Article
- Lysosomal peptidases-intriguing roles in cancer progression and neurodegeneration.FEBS open bio · 2022Review
- Low-level lysosomal membrane permeabilization for limited release and sublethal functions of cathepsin proteases in the cytosol and nucleus.FEBS open bio · 2022Review
- Regulatory role of cathepsin L in induction of nuclear laminopathy in Alzheimer's disease.Aging cell · 2022Article
- XPA is susceptible to proteolytic cleavage by cathepsin L during lysis of quiescent cells.DNA repair · 2022Article
- The Role of Cysteine Peptidases in Hematopoietic Stem Cell Differentiation and Modulation of Immune System Function.Frontiers in immunology · 2021Review
- Vitamin D in Triple-Negative and BRCA1-Deficient Breast Cancer-Implications for Pathogenesis and Therapy.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 2 countries.
Funding
Abstract
Loss of 53BP1 rescues BRCA1 deficiency and is associated with BRCA1-deficient and triple-negative breast cancers (TNBC) and with resistance to genotoxic drugs. The mechanisms responsible for decreased 53BP1 transcript and protein levels in tumors remain unknown. Here, we demonstrate that BRCA1 loss activates cathepsin L (CTSL)-mediated degradation of 53BP1. Activation of this pathway rescued homologous recombination repair and allowed BRCA1-deficient cells to bypass growth arrest. Importantly, depletion or inhibition of CTSL with vitamin D or specific inhibitors stabilized 53BP1 and increased genomic instability in response to radiation and poly(adenosine diphosphate-ribose) polymerase inhibitors, compromising proliferation. Analysis of human breast tumors identified nuclear CTSL as a positive biomarker for TNBC, which correlated inversely with 53BP1. Importantly, nuclear levels of CTSL, vitamin D receptor, and 53BP1 emerged as a novel triple biomarker signature for stratification of patients with BRCA1-mutated tumors and TNBC, with potential predictive value for drug response. We identify here a novel pathway with prospective relevance for diagnosis and customization of breast cancer therapy.
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What OpenQuestion holds
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.