دورية أكاديمية
Fatty Acid Synthase induced S6Kinase facilitates USP11-eIF4B complex formation for sustained oncogenic translation in DLBCL.
العنوان: | Fatty Acid Synthase induced S6Kinase facilitates USP11-eIF4B complex formation for sustained oncogenic translation in DLBCL. |
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المؤلفون: | Kapadia B; Department of Medicine, Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland, Baltimore, MD, 21201, USA., Nanaji NM; Department of Veteran Affairs, Maryland Healthcare System, Baltimore, MD 21201, USA.; University of Maryland Medical Center, Baltimore, MD, 21201, USA., Bhalla K; Department of Medicine, Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland, Baltimore, MD, 21201, USA., Bhandary B; Department of Medicine, Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland, Baltimore, MD, 21201, USA., Lapidus R; Department of Medicine, Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland, Baltimore, MD, 21201, USA., Beheshti A; Division of Hematology/Oncology, Molecular Oncology Research Institute, Tufts Medical Center, Boston, MA, 02111, USA., Evens AM; Division of Hematology/Oncology, Molecular Oncology Research Institute, Tufts Medical Center, Boston, MA, 02111, USA., Gartenhaus RB; Department of Medicine, Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland, Baltimore, MD, 21201, USA. rgartenhaus@som.umaryland.edu.; Veterans Administration Medical Center, Baltimore, MD, 21201, USA. rgartenhaus@som.umaryland.edu. |
المصدر: | Nature communications [Nat Commun] 2018 Feb 26; Vol. 9 (1), pp. 829. Date of Electronic Publication: 2018 Feb 26. |
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: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: [London] : Nature Pub. Group |
مواضيع طبية MeSH: | Gene Expression Regulation, Neoplastic* , Protein Biosynthesis*, Eukaryotic Initiation Factors/*genetics , Fatty Acid Synthase, Type I/*genetics , Ribosomal Protein S6 Kinases/*genetics , Thiolester Hydrolases/*genetics, Animals ; B-Lymphocytes/metabolism ; B-Lymphocytes/pathology ; Carcinogenesis/genetics ; Carcinogenesis/metabolism ; Carcinogenesis/pathology ; Cell Line, Tumor ; Eukaryotic Initiation Factors/metabolism ; Fatty Acid Synthase, Type I/metabolism ; Female ; Humans ; Lipid Metabolism/genetics ; Lymphoma, Large B-Cell, Diffuse/genetics ; Lymphoma, Large B-Cell, Diffuse/metabolism ; Lymphoma, Large B-Cell, Diffuse/pathology ; Mice ; Mice, Nude ; Neoplasm Transplantation ; Phosphatidylinositol 3-Kinases/genetics ; Phosphatidylinositol 3-Kinases/metabolism ; Phosphorylation ; Protein Binding ; Proto-Oncogene Proteins c-akt/genetics ; Proto-Oncogene Proteins c-akt/metabolism ; Ribosomal Protein S6 Kinases/metabolism ; Signal Transduction ; TOR Serine-Threonine Kinases/genetics ; TOR Serine-Threonine Kinases/metabolism ; Thiolester Hydrolases/metabolism |
مستخلص: | Altered lipid metabolism and aberrant protein translation are strongly associated with cancerous outgrowth; however, the inter-regulation of these key processes is still underexplored in diffuse large B-cell lymphoma (DLBCL). Although fatty acid synthase (FASN) activity is reported to positively correlate with PI3K-Akt-mTOR pathway that can modulate protein synthesis, the precise impact of FASN inhibition on this process is still unknown. Herein, we demonstrate that attenuating FASN expression or its activity significantly reduces eIF4B (eukaryotic initiation factor 4B) levels and consequently overall protein translation. Through biochemical studies, we identified eIF4B as a bonafide substrate of USP11, which stabilizes and enhances eIF4B activity. Employing both pharmacological and genetic approaches, we establish that FASN-induced PI3K-S6Kinase signaling phosphorylates USP11 enhancing its interaction with eIF4B and thereby promoting oncogenic translation. |
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معلومات مُعتمدة: | I01 BX002990 United States BX BLRD VA; R01 CA164311 United States CA NCI NIH HHS |
المشرفين على المادة: | 0 (Eukaryotic Initiation Factors) 0 (USP11 protein, human) 0 (eIF-4B) EC 2.3.1.85 (FASN protein, human) EC 2.3.1.85 (Fatty Acid Synthase, Type I) EC 2.7.1.1 (MTOR protein, human) EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) EC 2.7.11.1 (Ribosomal Protein S6 Kinases) EC 2.7.11.1 (TOR Serine-Threonine Kinases) EC 3.1.2.- (Thiolester Hydrolases) |
تواريخ الأحداث: | Date Created: 20180228 Date Completed: 20181121 Latest Revision: 20230814 |
رمز التحديث: | 20240628 |
مُعرف محوري في PubMed: | PMC5827760 |
DOI: | 10.1038/s41467-018-03028-y |
PMID: | 29483509 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2041-1723 |
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DOI: | 10.1038/s41467-018-03028-y |