2. Academic Validation
  3. Crosstalk between YAP-TEAD and PPAR suppresses HIV-1 LTR transcription in vitro

Crosstalk between YAP-TEAD and PPAR suppresses HIV-1 LTR transcription in vitro

  • Biochem Pharmacol. 2025 Oct:240:117109. doi: 10.1016/j.bcp.2025.117109.
Chenliang Zhou 1,  Xiaolian Liu 2,  Hong He 3,  Ziyao Wu 3,  Yihe Liu 3,  Huba Khamis Rashid 3,  Lin Li 4
Affiliations

Affiliations

  • 1 Key Laboratory of Infectious Diseases Research in South China, Ministry of Education, NMPA Key Laboratory for Research and Evaluation of Drug Metabolism, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, PR China; College of Pharmacy, Nanchang Medical College, Nanchang 330052, PR China.
  • 2 The Affiliated Eye Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, PR China.
  • 3 Key Laboratory of Infectious Diseases Research in South China, Ministry of Education, NMPA Key Laboratory for Research and Evaluation of Drug Metabolism, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, PR China.
  • 4 Key Laboratory of Infectious Diseases Research in South China, Ministry of Education, NMPA Key Laboratory for Research and Evaluation of Drug Metabolism, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, PR China. Electronic address: li75lin@126.com.
PMID: 40619008 DOI: 10.1016/j.bcp.2025.117109
Abstract

The regulation of HIV-1 transcription is a complex process influenced by host cellular factors and signaling pathways. In this study, we identified Yes-associated protein (YAP) as a novel negative regulator of HIV-1 long terminal repeat (LTR) activity, with the TEAD-binding domain (TBD) of YAP playing a pivotal role in this repression. Mechanistically, YAP suppresses HIV-1 LTR-driven transcription by interacting with the NF-κB binding motif within the LTR, mediated by its downstream TEAD proteins. Notably, our findings reveal that the crosstalk between YAP-TEAD and Peroxisome Proliferator-activated Receptor (PPAR) further modulates HIV-1 LTR transcription, with PPARγ inhibitors reversing YAP-mediated suppression. We show that both YAP and PPAR contribute to the repression of HIV-1 transcription through distinct but complementary mechanisms. This study highlights a previously unrecognized regulatory pathway involving YAP-TEAD-PPAR signaling that suppresses HIV-1 transcription and provides potential new targets for therapeutic intervention.

Keywords

HIV-1 LTR; NF-κB pathway; PPAR; TEAD; YAP.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-16578
    99.79%, PPARγ Antagonist