ArticleMolecular and cellular biology2002
Notch signaling induces rapid degradation of achaete-scute homolog 1.
Article in Molecular and cellular biology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
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Who cites it
81 citing papers in PubMed, 169 citations in OpenAlex.
- NOTCH1 reverses immune suppression in small cell lung cancer through reactivation of STING.The Journal of clinical investigation · 2025Trial
- NFIB Regulates Chemoresistance in Small Cell Lung Cancer by Suppressing Notch Signaling Activity.Cancer reports (Hoboken, N.J.) · 2026Article
- Updated Insights into the Molecular Pathophysiology of Olfactory Neuroblastoma Using Multi-Omics Analysis.Journal of personalized medicine · 2025Review
- Cell fate acquisition and reprogramming by the proneural transcription factor ASCL1.Open biology · 2025Review
- Review
- The next frontier in lung development and regeneration research: harnessing iPSC models to illuminate notch signaling pathways.Frontiers in cell and developmental biology · 2025Review
- Role of Notch1 Signaling Pathway in Small Cell Lung Carcinoma.Iranian journal of pathology · 2024Review
- Actionable Driver Events in Small Cell Lung Cancer.International journal of molecular sciences · 2023Review
- Multivalent state transitions shape the intratumoral composition of small cell lung carcinoma.Science advances · 2022Article
- Targeting Lysine-Specific Demethylase 1 Rescues Major Histocompatibility Complex Class I Antigen Presentation and Overcomes Programmed Death-Ligand 1 Blockade Resistance in SCLC.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2022Article
- A conserved YAP/Notch/REST network controls the neuroendocrine cell fate in the lungs.Nature communications · 2022Article
- Killing SCLC: insights into how to target a shapeshifting tumor.Genes & development · 2022Review
- Plasticity in the Absence of NOTCH Uncovers a RUNX2-Dependent Pathway in Small Cell Lung Cancer.Cancer research · 2022Article
- Homodimeric and Heterodimeric Interactions among Vertebrate Basic Helix-Loop-Helix Transcription Factors.International journal of molecular sciences · 2021Review
- Review
- Advances in Small-Cell Lung Cancer (SCLC) Translational Research.Cold Spring Harbor perspectives in medicine · 2021Review
- New Insights Into the Intricacies of Proneural Gene Regulation in the Embryonic and Adult Cerebral Cortex.Frontiers in molecular neuroscience · 2021Review
- Notch Signaling in Thyroid Cancer.Advances in experimental medicine and biology · 2021Review
- Article
- Effect of genetic variation in Notch regulator DTX1 on SCLC prognosis compared with the effect on NSCLC prongosis.Thoracic cancer · 2020Article
21 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
In neural development, Notch signaling plays a key role in restricting neuronal differentiation, promoting the maintenance of progenitor cells. Classically, Notch signaling causes transactivation of Hairy-enhancer of Split (HES) genes which leads to transcriptional repression of neural determination and differentiation genes. We now report that in addition to its known transcriptional mechanism, Notch signaling also leads to rapid degradation of the basic helix-loop-helix (bHLH) transcription factor human achaete-scute homolog 1 (hASH1). Using recombinant adenoviruses expressing active Notch1 in small-cell lung cancer cells, we showed that the initial appearance of Notch1 coincided with the loss of hASH1 protein, preceding the full decay of hASH1 mRNA. Overexpression of HES1 alone was capable of down-regulating hASH1 mRNA but could not replicate the acute reduction of hASH1 protein induced by Notch1. When adenoviral hASH1 was coinfected with Notch1, we still observed a dramatic and abrupt loss of the exogenous hASH1 protein, despite high levels of ongoing hASH1 RNA expression. Notch1 treatment decreased the apparent half-life of the adenoviral hASH1 protein and increased the fraction of hASH1 which was polyubiquitinylated. The proteasome inhibitor MG132 reversed the Notch1-induced degradation. The Notch RAM domain was dispensable but a lack of the OPA and PEST domains inactivated this Notch1 action. Overexpression of the hASH1-dimerizing partner E12 could protect hASH1 from degradation. This novel function of activated Notch to rapidly degrade a class II bHLH protein may prove to be important in many contexts in development and in 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.