{"doi":"10.1101/2020.05.21.108316","title":"ABHD17 enzymes regulate dynamic plasma membrane palmitoylation and N-Ras-dependent cancer growth","abstract":"A subset of 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 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 to Palmostatin 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 MEK inhibition. Our findings uncover a surprisingly restricted role for ABHD17 enzymes in modulating the N-Ras palmitoylation cycle and suggest that ABHD17 inhibitors may have value as targeted therapies for NRAS -mutant cancers.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":124905,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9581,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":338597,"name":"Radu M. Suciu","orcid":null,"position":1,"is_corresponding":false},{"id":338595,"name":"Noemi A. Zambetti","orcid":null,"position":2,"is_corresponding":false},{"id":570597,"name":"Thomas W. Hanigan","orcid":null,"position":3,"is_corresponding":false},{"id":17675,"name":"Ari J. Firestone","orcid":"0000-0001-9902-443X","position":4,"is_corresponding":false},{"id":225908,"name":"Anagha Inguva Sheth","orcid":"0000-0001-8201-2387","position":5,"is_corresponding":false},{"id":570598,"name":"Amy C. Long","orcid":null,"position":6,"is_corresponding":false},{"id":333482,"name":"Nhi Ngo","orcid":"0000-0001-9230-4308","position":7,"is_corresponding":false},{"id":333483,"name":"Kenneth M. Lum","orcid":"0000-0002-5955-9576","position":8,"is_corresponding":false},{"id":335398,"name":"Cassandra L. Henry","orcid":null,"position":9,"is_corresponding":false},{"id":570599,"name":"Stewart K. Richardson","orcid":null,"position":10,"is_corresponding":false},{"id":337817,"name":"Marina Predovic","orcid":"0000-0002-5201-3247","position":11,"is_corresponding":false},{"id":570158,"name":"Ben Huang","orcid":"0000-0003-2838-6315","position":12,"is_corresponding":false},{"id":354273,"name":"Amy R. Howell","orcid":"0000-0003-1958-6411","position":13,"is_corresponding":false},{"id":333484,"name":"Micah J. Niphakis","orcid":"0000-0001-9091-3679","position":14,"is_corresponding":false},{"id":337819,"name":"Kevin Shannon","orcid":"0000-0003-4299-1773","position":15,"is_corresponding":false},{"id":236419,"name":"Benjamin F. Cravatt","orcid":"0000-0001-5330-3492","position":16,"is_corresponding":false},{"id":337814,"name":"Jarrett R. Remsberg","orcid":"0000-0002-5234-0168","position":0,"is_corresponding":true}],"reference_count":67,"raw_metadata":null,"created_at":"2026-07-18T23:15:11.632153Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}