{"doi":"10.1021/acs.jproteome.3c00162","title":"Quantitative Proteomics of the CDK9 Interactome Reveals a Function of the HSP90-CDC37-P-TEFb Complex for BETi-Induced HIV-1 Latency Reactivation","abstract":"Brd4 has been intensively investigated as a promising drug target because of its implicated functions in oncogenesis, inflammation, and HIV-1 transcription. The formation of the Brd4-P-TEFb (CDK9/Cyclin T1) complex and its regulation of transcriptional elongation are critical for HIV latency reactivation and expression of many oncogenes. To further investigate the mechanism of the Brd4-P-TEFb complex in controlling elongation, mass spectrometry-based quantitative proteomics of the CDK9 interactome was performed. Upon treatment with the selective BET bromodomain inhibitor JQ1, 352 proteins were successfully identified with high confidence as CDK9-interacting proteins. Among them, increased bindings of HSP90 and CDC37 to CDK9 were particularly striking, and our data suggest that the HSP90-CDC37-P-TEFb complex is involved in controlling the dynamic equilibrium of the P-TEFb complex during BETi-induced reactivation of HIV-1 latency. Furthermore, the HSP90-CDC37-P-TEFb complex directly regulates HIV-1 transcription and relies on recruitment by heat shock factor 1 (HSF1) for binding to the HIV-1 promoter. These results advance the understanding of HSP90-CDC37-P-TEFb in HIV-1 latency reversal and enlighten the development of potential strategies to eradicate HIV-1 using a combination of targeted drugs.","journal":"Journal of Proteome Research","year":2023,"id":385227,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9504,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":487973,"name":"Chunjing Chen","orcid":"0009-0009-1270-6530","position":1,"is_corresponding":false},{"id":1152950,"name":"Zhenrui Pan","orcid":"0000-0002-0355-5197","position":2,"is_corresponding":false},{"id":1152951,"name":"Yaohui He","orcid":"0000-0002-8235-8924","position":3,"is_corresponding":false},{"id":1153341,"name":"Zhanming Zhang","orcid":null,"position":4,"is_corresponding":false},{"id":1152952,"name":"Rongdiao Liu","orcid":"0000-0002-3802-3561","position":5,"is_corresponding":false},{"id":406265,"name":"Yuhua Xue","orcid":"0000-0001-5804-5162","position":6,"is_corresponding":false},{"id":406267,"name":"Qiang Zhou","orcid":"0000-0001-7202-3947","position":7,"is_corresponding":false},{"id":406266,"name":"Xiang Gao","orcid":"0000-0002-3774-1852","position":8,"is_corresponding":false},{"id":407691,"name":"Cong Wang","orcid":"0000-0003-2626-9596","position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":null,"created_at":"2026-07-19T01:17:48.629718Z","pmid":"37540094","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":[]}