Quantitative proteomics of the CDK9 interactome reveals a novel 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 is 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 (BETi) JQ1, 535 proteins were successfully identified with high confidence as CDK9-interacting proteins. Among them, that 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 P-TEFb’s dynamic equilibrium during BETi-induced HIV-1 latency reactivation. Furthermore, the HSP90-CDC37-P-TEFb complex directly regulates HIV-1 transcription and relies on the 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..
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Preprint| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
bioRxiv.org - (2024) vom: 23. Apr. Zur Gesamtaufnahme - year:2024 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wang, Cong [VerfasserIn] |
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| doi: |
10.1101/2022.01.20.477160 |
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| PPN (Katalog-ID): |
XBI035047712 |
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| 245 | 1 | 0 | |a Quantitative proteomics of the CDK9 interactome reveals a novel function of the HSP90-CDC37-P-TEFb complex for BETi-induced HIV-1 latency reactivation |
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| 520 | |a 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 is 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 (BETi) JQ1, 535 proteins were successfully identified with high confidence as CDK9-interacting proteins. Among them, that 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 P-TEFb’s dynamic equilibrium during BETi-induced HIV-1 latency reactivation. Furthermore, the HSP90-CDC37-P-TEFb complex directly regulates HIV-1 transcription and relies on the 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. | ||
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| 700 | 1 | |a He, Yaohui |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Zhanming |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Rongdiao |e verfasserin |4 aut | |
| 700 | 1 | |a Xue, Yuhua |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Qiang |e verfasserin |4 aut | |
| 700 | 1 | |a Gao, Xiang |e verfasserin |4 aut | |
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