ArticleMolecular biology reports2012
ATF4 orchestrates a program of BH3-only protein expression in severe hypoxia.
Article in Molecular biology reports, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 35 citations in OpenAlex.
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- An integrative systems biology approach to overcome venetoclax resistance in acute myeloid leukemia.PLoS computational biology · 2022Article
- Targeting mitochondrial respiration and the BCL2 family in high-grade MYC-associated B-cell lymphoma.Molecular oncology · 2022Article
- A New Player in Neuroblastoma: YAP and Its Role in the Neuroblastoma Microenvironment.Cancers · 2021Review
- Roles of interacting stress-related genes in lifespan regulation: insights for translating experimental findings to humans.Journal of translational genetics and genomics · 2021Article
- Neddylation: A Versatile Pathway Takes on Chronic Liver Diseases.Frontiers in medicine · 2020Review
- Identification of transcription factors that regulateAutophagy · 2020Article
- PRMT1 suppresses ATF4-mediated endoplasmic reticulum response in cardiomyocytes.Cell death & disease · 2019Article
- Dual role of Endoplasmic Reticulum Stress-Mediated Unfolded Protein Response Signaling Pathway in Carcinogenesis.International journal of molecular sciences · 2019Review
- Targeting Mitochondrial Structure Sensitizes Acute Myeloid Leukemia to Venetoclax Treatment.Cancer discovery · 2019Article
- Tocotrienols Modulate a Life or Death Decision in Cancers.International journal of molecular sciences · 2019Review
- Protein neddylation and its alterations in human cancers for targeted therapy.Cellular signalling · 2018Review
- Global, Survival, and Apoptotic Transcriptome during Mouse and Human Early Embryonic Development.BioMed research international · 2018Article
- Assessing Autophagic Flux by Measuring LC3, p62, and LAMP1 Co-localization Using Multispectral Imaging Flow Cytometry.Journal of visualized experiments : JoVE · 2017Article
- How to control self-digestion: transcriptional, post-transcriptional, and post-translational regulation of autophagy.Trends in cell biology · 2015Review
- Metabolic and hypoxic adaptation to anti-angiogenic therapy: a target for induced essentiality.EMBO molecular medicine · 2015Review
- Hepatitis C virus core protein activates autophagy through EIF2AK3 and ATF6 UPR pathway-mediated MAP1LC3B and ATG12 expression.Autophagy · 2014Article
- The return of the nucleus: transcriptional and epigenetic control of autophagy.Nature reviews. Molecular cell biology · 2014Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Intratumoral hypoxia is associated with poor prognosis, regardless of the mode of therapy. Cancer cells survive this condition through activating several adaptive signaling pathways, including the integrated stress response (ISR) and autophagy. Activating transcription factor 4 (ATF4) is the major transcriptional mediator of the ISR, which we have shown to be involved in autophagy regulation to protect cells from severe hypoxia. Here we demonstrate that ATF4 orchestrates a program of BH3-only protein expression in severe hypoxia. We find that the BH3-only proteins HRK, PUMA, and NOXA are transcriptionally induced in severe hypoxia and that their expression is abrogated by RNA interference against ATF4. In particular, we show that the BH3-only protein harakiri (HRK) is transactivated by ATF4 in severe hypoxia through direct binding of ATF4 to the promoter region. Furthermore, we demonstrate through siRNA knockdown that HRK induces autophagy and promotes cancer cell survival in severe hypoxia.
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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.