دورية أكاديمية
أعرض في EDS

ABL kinases regulate the stabilization of HIF-1α and MYC through CPSF1.

التفاصيل البيبلوغرافية
العنوان: ABL kinases regulate the stabilization of HIF-1α and MYC through CPSF1.
المؤلفون: Mayro B; Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC 27710., Hoj JP; Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC 27710., Cerda-Smith CG; Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC 27710., Hutchinson HM; Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC 27710., Caminear MW; Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC 27710., Thrash HL; Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC 27710., Winter PS; Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC 27710., Wardell SE; Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC 27710., McDonnell DP; Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC 27710.; Duke Cancer Institute, Duke University School of Medicine, Durham, NC 27710., Wu C; Department of Orthopedic Surgery, Duke University School of Medicine, Durham, NC 27710., Wood KC; Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC 27710.; Duke Cancer Institute, Duke University School of Medicine, Durham, NC 27710., Pendergast AM; Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC 27710.; Duke Cancer Institute, Duke University School of Medicine, Durham, NC 27710.
المصدر: Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2023 Apr 18; Vol. 120 (16), pp. e2210418120. Date of Electronic Publication: 2023 Apr 11.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.
اللغة: English
بيانات الدورية: Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1091-6490 (Electronic) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington, DC : National Academy of Sciences
مواضيع طبية MeSH: Gene Expression Regulation* , Transcription Factors*/metabolism, Humans ; Cullin Proteins/metabolism ; Hypoxia ; Phosphorylation ; Protein Serine-Threonine Kinases/metabolism ; Ubiquitin-Protein Ligases/metabolism ; Genes, abl ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Proto-Oncogene Proteins c-myc/metabolism ; Cleavage And Polyadenylation Specificity Factor/metabolism
مستخلص: 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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معلومات مُعتمدة: R01 HL151782 United States HL NHLBI NIH HHS; K00 CA245732 United States CA NCI NIH HHS; F31 CA243293 United States CA NCI NIH HHS; F99 CA264162 United States CA NCI NIH HHS; R01 CA263593 United States CA NCI NIH HHS; R01 CA266389 United States CA NCI NIH HHS; F30 CA247323 United States CA NCI NIH HHS; R01 CA246133 United States CA NCI NIH HHS; P30 CA014236 United States CA NCI NIH HHS; T32 GM145449 United States GM NIGMS NIH HHS; T32 GM007105 United States GM NIGMS NIH HHS; T32 GM007171 United States GM NIGMS NIH HHS
فهرسة مساهمة: Keywords: ABL kinases; CPSF1; E3-ligase; HIF-1α; MYC
المشرفين على المادة: 0 (CUL4A protein, human)
0 (Cullin Proteins)
EC 2.7.11.1 (Protein Serine-Threonine Kinases)
0 (Transcription Factors)
EC 2.3.2.27 (Ubiquitin-Protein Ligases)
0 (Hypoxia-Inducible Factor 1, alpha Subunit)
0 (Proto-Oncogene Proteins c-myc)
0 (Cleavage And Polyadenylation Specificity Factor)
تواريخ الأحداث: Date Created: 20230411 Date Completed: 20230414 Latest Revision: 20240216
رمز التحديث: 20240216
مُعرف محوري في PubMed: PMC10120083
DOI: 10.1073/pnas.2210418120
PMID: 37040401
قاعدة البيانات: MEDLINE
الوصف
تدمد:1091-6490
DOI:10.1073/pnas.2210418120