{"doi":"10.1016/j.celrep.2024.114033","title":"The Legionella pneumophila effector DenR hijacks the host NRas proto-oncoprotein to downregulate MAPK signaling","abstract":"Small GTPases of the Ras subfamily are best known for their role as proto-oncoproteins, while their function during microbial infection has remained elusive. Here, we show that Legionella pneumophila hijacks the small GTPase NRas to the Legionella-containing vacuole (LCV) surface. A CRISPR interference screen identifies a single L. pneumophila effector, DenR (Lpg1909), required for this process. Recruitment is specific for NRas, while its homologs KRas and HRas are excluded from LCVs. The C-terminal hypervariable tail of NRas is sufficient for recruitment, and interference with either NRas farnesylation or S-acylation sites abrogates recruitment. Intriguingly, we detect markers of active NRas signaling on the LCV, suggesting it acts as a signaling platform. Subsequent phosphoproteomics analyses show that DenR rewires the host NRas signaling landscape, including dampening of the canonical mitogen-activated protein kinase pathway. These results provide evidence for L. pneumophila targeting NRas and suggest a link between NRas GTPase signaling and microbial infection.","journal":"Cell Reports","year":2024,"id":455612,"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":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9509,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":236475,"name":"Chad D. Williamson","orcid":"0000-0003-4886-5102","position":1,"is_corresponding":false},{"id":275521,"name":"Trisha Tucholski","orcid":"0000-0003-1407-6922","position":2,"is_corresponding":false},{"id":570747,"name":"Nicole A. Ellis","orcid":"0000-0001-9592-8415","position":3,"is_corresponding":false},{"id":1280151,"name":"Sabrina Bouchard","orcid":null,"position":4,"is_corresponding":false},{"id":321537,"name":"Michal Jarník","orcid":"0000-0002-1269-3508","position":5,"is_corresponding":false},{"id":1280152,"name":"M.J. Allen","orcid":null,"position":6,"is_corresponding":false},{"id":400352,"name":"Aleksandra Nita‐Lazar","orcid":"0000-0002-8523-605X","position":7,"is_corresponding":false},{"id":341969,"name":"Matthias P. Machner","orcid":"0000-0002-6971-7451","position":8,"is_corresponding":false},{"id":355588,"name":"Stephanie S. Lehman","orcid":"0000-0002-4568-3082","position":0,"is_corresponding":true}],"reference_count":71,"raw_metadata":null,"created_at":"2026-07-19T02:03:22.974789Z","pmid":"38568811","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":[]}