{"doi":"10.1101/2021.09.17.460854","title":"A p53-Phosphoinositide Signalosome Regulates Nuclear Akt Activation","abstract":"Abstract The tumor suppressor p53 and the phosphoinositide 3-kinase (PI3K)-Akt pathway have fundamental roles in regulating cell growth, apoptosis and are frequently mutated in cancer. Here, we show that genotoxic stress induces nuclear Akt activation by a p53-dependent mechanism that is independent from the canonical membrane-localized PI3K-Akt pathway. Upon genotoxic stress a nuclear p53-PI3,4,5P 3 complex is generated in regions devoid of membranes by a nuclear PI3K, and this complex recruits all the kinases required to activate Akt and phosphorylate FOXOs, inhibiting DNA damage-induced apoptosis. Wild-type p53 activates nuclear Akt in an on/off fashion upon stress, whereas mutant p53 stimulates high basal Akt activity, indicating a fundamental difference. The nuclear p53-phosphoinositide signalosome is distinct from the canonical membrane-localized pathway and insensitive to PI3K inhibitors currently in the clinic, underscoring its therapeutic relevance. In brief p53 assembles a PI3K-Akt pathway that regulates nuclear Akt activation independent of the canonical pathway on membranes.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":214417,"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":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9516,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":335622,"name":"Suyong Choi","orcid":null,"position":1,"is_corresponding":false},{"id":334119,"name":"Tianmu Wen","orcid":"0009-0002-2495-5488","position":2,"is_corresponding":false},{"id":807851,"name":"Changliang Chen","orcid":"0000-0002-6495-1740","position":3,"is_corresponding":false},{"id":335621,"name":"Narendra Thapa","orcid":null,"position":4,"is_corresponding":false},{"id":285809,"name":"Vincent L. Cryns","orcid":"0000-0003-0355-2268","position":5,"is_corresponding":false},{"id":334121,"name":"Richard A. Anderson","orcid":"0000-0001-6265-8359","position":6,"is_corresponding":false},{"id":807850,"name":"Mo Chen","orcid":"0000-0001-7226-6789","position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":null,"created_at":"2026-07-18T23:52:46.604690Z","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":[]}