{"doi":"10.1101/2021.03.15.435375","title":"The PfAP2-HS transcription factor protects malaria parasites from febrile temperatures","abstract":"Periodic fever is the most characteristic clinical feature of human malaria 1-3 , but how parasites survive febrile episodes is not known. While Plasmodium spp. genomes encode a full complement of chaperones 4 , they lack an ortholog of the conserved transcription factor HSF1, which in most eukaryotes activates the expression of key chaperones upon heat shock (HS) 5-8 . Here we identified PfAP2-HS, a transcription factor of the ApiAP2 family 9-11 , as the key regulator of the P. falciparum protective HS response. The PfAP2-HS-dependent HS response is largely restricted to rapid activation of hsp70-1 , the predominant direct target of PfAP2-HS, and hsp90 . Deletion of PfAP2-HS dramatically reduced HS survival and also resulted in severe growth defects at 37°C, but not at 35°C, and increased sensitivity to imbalances in protein homeostasis (proteostasis) produced by artemisinin, the current frontline antimalarial drug 12,13 . These results demonstrate that PfAP2-HS contributes to general maintenance of proteostasis and drives a rapid chaperone-based protective response against febrile temperatures. While several ApiAP2 transcription factors regulate life cycle transitions in malaria parasites 11,14,15 , PfAP2-HS is the first identified Plasmodium transcription factor that controls a protective response to a within-host environmental challenge.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":220426,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.954,"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":819948,"name":"Lucas Michel-Todó","orcid":"0000-0003-2098-4302","position":1,"is_corresponding":false},{"id":245294,"name":"Timothy J. Russell","orcid":"0000-0001-6651-6366","position":2,"is_corresponding":false},{"id":819949,"name":"Núria Casas-Vila","orcid":"0000-0003-4233-0529","position":3,"is_corresponding":false},{"id":623670,"name":"David J. Conway","orcid":"0000-0002-8711-3037","position":4,"is_corresponding":false},{"id":686096,"name":"Zbynek Bozdech","orcid":"0000-0002-9830-8446","position":5,"is_corresponding":false},{"id":245298,"name":"Manuel Llinás","orcid":"0000-0002-6173-5882","position":6,"is_corresponding":false},{"id":819950,"name":"Alfred Cortés","orcid":"0000-0003-0730-6582","position":7,"is_corresponding":false},{"id":819947,"name":"Elisabet Tintó-Font","orcid":"0000-0002-5770-0556","position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":null,"created_at":"2026-07-18T23:53:46.965811Z","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":[]}