ArticleProceedings of the National Academy of Sciences of the United States of America2023
ABL kinases regulate the stabilization of HIF-1α and MYC through CPSF1.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.
What it found
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Who cites it
7 citing papers in PubMed, 1 synthesis or guideline pooled it, 10 citations in OpenAlex.
- The Role of c-Abl in Alzheimer's Disease: Guilty or not Guilty?Cellular and molecular neurobiology · 2025Pooled it
- ABL kinase inactivation induces transcription-replication conflicts and impairs replication fork progression in metastatic small cell lung cancer.Cell reports · 2026Article
- Oncogenic SOX9-TRAIP signaling drives gastric cancer progression by mediating the degradation of the CPEB3-mTORC1 tumor suppressor axis.World journal of surgical oncology · 2026Article
- EGLN1 (PHD2) role in tumor microenvironment: insights for therapeutic targeting.Experimental & molecular medicine · 2025Review
- Use of antibodies against Epstein-Barr virus nuclear antigen 1 for detection of cellular proteins with monomethylated arginine residues that are potentially involved in viral transformation.Archives of virology · 2024Article
- Mutant TP53 promotes invasion of lung cancer cells by regulating desmoglein 3.Journal of cancer research and clinical oncology · 2024Article
- Article
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
The hypoxia-inducible factor 1-α (HIF-1α) enables cells to adapt and respond to hypoxia (Hx), and the activity of this transcription factor is regulated by several oncogenic signals and cellular stressors. While the pathways controlling normoxic degradation of HIF-1α are well understood, the mechanisms supporting the sustained stabilization and activity of HIF-1α under Hx are less clear. We report that ABL kinase activity protects HIF-1α from proteasomal degradation during Hx. Using a fluorescence-activated cell sorting (FACS)-based CRISPR/Cas9 screen, we identified HIF-1α as a substrate of the cleavage and polyadenylation specificity factor-1 (CPSF1), an E3-ligase which targets HIF-1α for degradation in the presence of an ABL kinase inhibitor in Hx. We show that ABL kinases phosphorylate and interact with CUL4A, a cullin ring ligase adaptor, and compete with CPSF1 for CUL4A binding, leading to increased HIF-1α protein levels. Further, we identified the MYC proto-oncogene protein as a second CPSF1 substrate and show that active ABL kinase protects MYC from CPSF1-mediated degradation. These studies uncover a role for CPSF1 in cancer pathobiology as an E3-ligase antagonizing the expression of the oncogenic transcription factors, HIF-1α and MYC.
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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 Socratic graph.