{"doi":"10.26508/lsa.202403147","title":"DAF-18/PTEN protects LIN-35/Rb from CLP-1/CAPN-mediated cleavage to promote starvation resistance","abstract":"Starvation resistance is a fundamental trait with profound influence on fitness and disease risk. DAF-18, the Caenorhabditis elegans ortholog of the tumor suppressor PTEN, promotes starvation resistance. PTEN is a dual phosphatase, and DAF-18 promotes starvation resistance as a lipid phosphatase by antagonizing insulin/IGF and PI3K signaling, activating the tumor suppressor DAF-16/FoxO. However, if or how DAF-18/PTEN protein-phosphatase activity promotes starvation resistance is unknown. Using genetic, genomic, bioinformatic, and biochemical approaches, we identified the C. elegans retinoblastoma/RB protein homolog, LIN-35/Rb, as a critical mediator of the effect of DAF-18/PTEN on starvation resistance. We show that DAF-18/PTEN protects LIN-35/Rb from cleavage by the μ-Calpain homolog CLP-1/CAPN, and that LIN-35/Rb together with the repressive DREAM complex promotes starvation resistance. We conclude that the tumor suppressors DAF-18/PTEN and LIN-35/Rb function in a linear pathway, with LIN-35/Rb and the rest of the DREAM complex functioning as a transcriptional effector of DAF-18/PTEN protein-phosphatase activity resulting in repression of germline gene expression. This work is significant for revealing a network of tumor suppressors that promote survival during cellular and developmental quiescence.","journal":"Life Science Alliance","year":2025,"id":552285,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":1,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9532,"is_data_producer":true,"deposit_databanks":{"GEO":["GSE281157"],"Dataset DOI":["https://github.com/jc271828/daf18_and_lin35"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":734468,"name":"Rojin Chitrakar","orcid":null,"position":1,"is_corresponding":false},{"id":653499,"name":"L. Ryan Baugh","orcid":"0000-0003-2148-5492","position":2,"is_corresponding":false},{"id":826631,"name":"Jingxian Chen","orcid":"0000-0002-1642-6060","position":0,"is_corresponding":true}],"reference_count":92,"raw_metadata":null,"created_at":"2026-07-19T02:54:33.203144Z","pmid":"40199585","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":[]}