{"doi":"10.17615/dxmr-vy81","title":"RhoE Is a Pro-Survival p53 Target Gene that Inhibits ROCK I-Mediated Apoptosis in Response to Genotoxic Stress","abstract":"The Rho family of GTPases regulates many aspects of cellular behavior through alterations to the actin cytoskeleton [1-6]. The majority of the Rho family proteins function as molecular switches cycling between the active, GTP-bound, and the inactive, GDP-bound, conformations [1-6]. Unlike typical Rho family proteins, the Rnd subfamily members, including Rnd1, Rnd2, RhoE/Rnd3, and RhoH, are GTPase deficient, and thus expected to be constitutively active [7-10]. Here, we identify an unexpected role for RhoE/Rnd3 in the regulation of the p53-mediated stress response. We show that RhoE is a transcriptional p53 target gene, and that genotoxic stress triggers actin depolymerization, resulting in actin-stress fiber disassembly through p53-dependent RhoE induction. Silencing of RhoE induction in response to genotoxic stress maintains stress fiber formation and strikingly increases apoptosis, implying an antagonistic role for RhoE in p53-dependent apoptosis. We found that RhoE inhibits ROCK I (Rho associated kinase I) activity during genotoxic stress thereby suppressing apoptosis. We demonstrate that the p53-mediated induction of RhoE in response to DNA damage favors cell survival partly through inhibition of ROCK I-mediated apoptosis. Thus, RhoE is anticipated to function by regulating ROCK I signaling to control the balance between cell survival and cell death in response to genotoxic stress.","journal":"UNC Libraries","year":2020,"id":111562,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9588,"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":268857,"name":"Sarah A. Boswell","orcid":"0000-0002-3118-3378","position":1,"is_corresponding":false},{"id":254947,"name":"Channing J. Der","orcid":"0000-0002-7751-2747","position":2,"is_corresponding":false},{"id":528968,"name":"Stuart A. Aaronson","orcid":"0000-0002-4643-0474","position":3,"is_corresponding":false},{"id":529813,"name":"Hyung-Gu Kim","orcid":null,"position":4,"is_corresponding":false},{"id":235912,"name":"Sam W. Lee","orcid":"0000-0002-4114-7338","position":5,"is_corresponding":false},{"id":528969,"name":"Anne J. Ridley","orcid":"0000-0001-8186-5708","position":6,"is_corresponding":false},{"id":324288,"name":"G. Paolo Dotto","orcid":"0000-0002-1197-8448","position":7,"is_corresponding":false},{"id":529814,"name":"Pat P. Ongusaha","orcid":null,"position":8,"is_corresponding":false},{"id":298024,"name":"Young‐Bum Kim","orcid":"0000-0001-9471-6330","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:13:05.597252Z","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":[]}