دورية أكاديمية
ABHD17 regulation of plasma membrane palmitoylation and N-Ras-dependent cancer growth.
| العنوان: | ABHD17 regulation of plasma membrane palmitoylation and N-Ras-dependent cancer growth. |
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| المؤلفون: | Remsberg JR; Department of Chemistry, The Scripps Research Institute, La Jolla, CA, USA., Suciu RM; Department of Chemistry, The Scripps Research Institute, La Jolla, CA, USA., Zambetti NA; Department of Pediatrics, University of California, San Francisco, San Francisco, CA, USA.; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA., Hanigan TW; Department of Chemistry, The Scripps Research Institute, La Jolla, CA, USA., Firestone AJ; Department of Pediatrics, University of California, San Francisco, San Francisco, CA, USA.; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA., Inguva A; Department of Pediatrics, University of California, San Francisco, San Francisco, CA, USA., Long A; Department of Pediatrics, University of California, San Francisco, San Francisco, CA, USA., Ngo N; Lundbeck La Jolla Research Center, Inc., San Diego, CA, USA., Lum KM; Lundbeck La Jolla Research Center, Inc., San Diego, CA, USA., Henry CL; Lundbeck La Jolla Research Center, Inc., San Diego, CA, USA., Richardson SK; Department of Chemistry, University of Connecticut, Storrs, CT, USA., Predovic M; Department of Pediatrics, University of California, San Francisco, San Francisco, CA, USA., Huang B; Department of Pediatrics, University of California, San Francisco, San Francisco, CA, USA.; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA., Dix MM; Department of Chemistry, The Scripps Research Institute, La Jolla, CA, USA., Howell AR; Department of Chemistry, University of Connecticut, Storrs, CT, USA., Niphakis MJ; Lundbeck La Jolla Research Center, Inc., San Diego, CA, USA. MIIP@lundbeck.com., Shannon K; Department of Pediatrics, University of California, San Francisco, San Francisco, CA, USA. Kevin.Shannon@ucsf.edu.; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA. Kevin.Shannon@ucsf.edu., Cravatt BF; Department of Chemistry, The Scripps Research Institute, La Jolla, CA, USA. cravatt@scripps.edu. |
| المصدر: | Nature chemical biology [Nat Chem Biol] 2021 Aug; Vol. 17 (8), pp. 856-864. Date of Electronic Publication: 2021 Apr 29. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Nature Pub. Group Country of Publication: United States NLM ID: 101231976 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1552-4469 (Electronic) Linking ISSN: 15524450 NLM ISO Abbreviation: Nat Chem Biol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: New York, NY : Nature Pub. Group, [2005]- |
| مواضيع طبية MeSH: | Cell Membrane/*metabolism , Hydrolases/*metabolism , Leukemia, Myeloid, Acute/*metabolism , Leukemia, Promyelocytic, Acute/*metabolism , ras Proteins/*metabolism, Cell Proliferation ; Cells, Cultured ; Humans ; Leukemia, Myeloid, Acute/pathology ; Leukemia, Promyelocytic, Acute/pathology ; Lipoylation ; Microsomes, Liver/chemistry ; Microsomes, Liver/metabolism ; Molecular Structure |
| مستخلص: | Multiple Ras proteins, including N-Ras, depend on a palmitoylation/depalmitoylation cycle to regulate their subcellular trafficking and oncogenicity. General lipase inhibitors such as Palmostatin M (Palm M) block N-Ras depalmitoylation, but lack specificity and target several enzymes displaying depalmitoylase activity. Here, we describe ABD957, a potent and selective covalent inhibitor of the ABHD17 family of depalmitoylases, and show that this compound impairs N-Ras depalmitoylation in human acute myeloid leukemia (AML) cells. ABD957 produced partial effects on N-Ras palmitoylation compared with Palm M, but was much more selective across the proteome, reflecting a plasma membrane-delineated action on dynamically palmitoylated proteins. Finally, ABD957 impaired N-Ras signaling and the growth of NRAS-mutant AML cells in a manner that synergizes with MAP kinase kinase (MEK) inhibition. Our findings uncover a surprisingly restricted role for ABHD17 enzymes as regulators of the N-Ras palmitoylation cycle and suggest that ABHD17 inhibitors may have value as targeted therapies for NRAS-mutant cancers. (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.) |
| التعليقات: | Comment in: Nat Chem Biol. 2021 Aug;17(8):840-841. doi: 10.1038/s41589-021-00789-4. (PMID: 33927410) |
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| معلومات مُعتمدة: | R01 CA238249 United States CA NCI NIH HHS; K08 CA256489 United States CA NCI NIH HHS; R01 NS073831 United States NS NINDS NIH HHS; R01 CA193994 United States CA NCI NIH HHS; R35 CA231991 United States CA NCI NIH HHS; R37 CA072614 United States CA NCI NIH HHS; R01 CA072614 United States CA NCI NIH HHS |
| المشرفين على المادة: | EC 3.- (ABHD17B protein, human) EC 3.- (Hydrolases) EC 3.6.5.2 (ras Proteins) |
| تواريخ الأحداث: | Date Created: 20210430 Date Completed: 20210907 Latest Revision: 20240608 |
| رمز التحديث: | 20240608 |
| مُعرف محوري في PubMed: | PMC8900659 |
| DOI: | 10.1038/s41589-021-00785-8 |
| PMID: | 33927411 |
| قاعدة البيانات: | MEDLINE |
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| DOI: | 10.1038/s41589-021-00785-8 |