ArticleBlood2011
Notch/HES1-mediated PARP1 activation: a cell type-specific mechanism for tumor suppression.
Article in Blood, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00137111 (Total XV - Total Therapy Study XV for Newly Diagnosed Patients With Acute Lymphoblastic Leukemia), which is not on this map. Cited by 33 papers.
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.
Total XV - Total Therapy Study XV for Newly Diagnosed Patients With Acute Lymphoblastic Leukemia
Who cites it
33 citing papers in PubMed, 65 citations in OpenAlex.
- PARP-1 protein expression in glioblastoma multiforme.European journal of histochemistry : EJH · 2012Trial
- Vitamin D Attenuates Inflammation and Mitochondrial Dysfunction in Experimental Models Relevant to Connective Tissue Disease-Associated Pulmonary Arterial Hypertension.Food science & nutrition · 2026Article
- Notch signaling in the tumor microenvironment: recent advances and targeted therapeutics.Molecular cancer · 2026Review
- E-Cadherin Regulates HIF1-α In Vitro in Induced 3D Spheroid Models of Human Breast Cancer Through Both mTOR and Notch1 Signaling.Biomedicines · 2025Article
- iNOS-Produced Nitric Oxide from Cancer Cells as an Intermediate of Stemness Regulation by PARP-1 in Colorectal Cancer.Biomolecules · 2025Article
- Expression of nicastrin, NICD1, and Hes1 in NCSTN knockout mice: implications for hidradenitis suppurativa, Alzheimer's, and liver cancer.European journal of medical research · 2024Article
- Notch signaling pathway in cancer: from mechanistic insights to targeted therapies.Signal transduction and targeted therapy · 2024Review
- Pamiparib Induces Neurodevelopmental Defects and Cerebral Haemorrhage in Zebrafish Embryos via Inhibiting Notch Signalling.Molecular neurobiology · 2022Article
- Construction of a B cell-related gene pairs signature for predicting prognosis and immunotherapeutic response in non-small cell lung cancer.Frontiers in immunology · 2022Article
- RAG1 co-expression signature identifies ETV6-RUNX1-like B-cell precursor acute lymphoblastic leukemia in children.Cancer medicine · 2021Article
- Poly (ADP-Ribose) Polymerase 1 Protein Expression in Normal Pancreas and Pancreatic Adenocarcinoma.Case reports in gastrointestinal medicine · 2020Article
- Antileukemia Effects of Notch-Mediated Inhibition of Oncogenic PLK1 in B-Cell Acute Lymphoblastic Leukemia.Molecular cancer therapeutics · 2019Article
- Notch signaling activation induces cell death in MAPKi-resistant melanoma cells.Pigment cell & melanoma research · 2019Article
- Article
- Notch signaling pathway mediates Doxorubicin-driven apoptosis in cancers.Cancer management and research · 2018Article
- Xeroderma Pigmentosa Group A (XPA), Nucleotide Excision Repair and Regulation by ATR in Response to Ultraviolet Irradiation.Advances in experimental medicine and biology · 2017Review
- Novel drug targets for personalized precision medicine in relapsed/refractory diffuse large B-cell lymphoma: a comprehensive review.Molecular cancer · 2015Review
- Review
- Article
- PARP-1 and CASP3 genes are up-regulated in LNCaP and PC-3 prostate cancer cell lines.Human cell · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Notch signaling plays both oncogenic and tumor suppressor roles, depending on cell type. In contrast to T-cell acute lymphoblastic leukemia (ALL), where Notch activation promotes leukemogenesis, induction of Notch signaling in B-cell ALL (B-ALL) leads to growth arrest and apoptosis. The Notch target Hairy/Enhancer of Split1 (HES1) is sufficient to reproduce this tumor suppressor phenotype in B-ALL; however, the mechanism is not yet known. We report that HES1 regulates proapoptotic signals by the novel interacting protein Poly ADP-Ribose Polymerase1 (PARP1) in a cell type-specific manner. Interaction of HES1 with PARP1 inhibits HES1 function, induces PARP1 activation, and results in PARP1 cleavage in B-ALL. HES1-induced PARP1 activation leads to self-ADP ribosylation of PARP1, consumption of nicotinamide adenine dinucleotide(+), diminished adenosine triphosphate levels, and translocation of apoptosis-inducing factor from mitochondria to the nucleus, resulting in apoptosis in B-ALL but not T-cell ALL. Importantly, induction of Notch signaling by the Notch agonist peptide Delta/Serrate/Lag-2 can reproduce these events and leads to B-ALL apoptosis. The novel interaction of HES1 and PARP1 in B-ALL modulates the function of the HES1 transcriptional complex and signals through PARP1 to induce apoptosis. This mechanism shows a cell type-specific proapoptotic pathway that may lead to Notch agonist-based cancer therapeutics.
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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.