A Novel Small-Molecule GRP94 Modulator Increases PCSK9 Secretion and Promotes LDLR Degradation
Abstract
1. Introduction
2. Materials and Methods
3. Results
3.1. cp153 Inhibits ER-Associated Protein Dislocation and Substrate Ubiquitination
3.2. cp153 Inhibits Ubiquitination and Stabilizes ERAD Substrates While Inducing ER Stress
3.3. GRP94 Is a Potential Target of cp153
3.4. cp153 Modulates PCSK9 Secretion and LDLR Degradation Without Inducing Cytosolic HSP90 Responses
3.5. cp153 Inhibits HeLa Cell Migration and Melanin Production
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
ER | Endoplasmic reticulum |
ERAD | ER-associated degradation |
CETSA | Cellular Thermal Shift Assay |
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Yan, W.; Zhong, Y.; Fang, S. A Novel Small-Molecule GRP94 Modulator Increases PCSK9 Secretion and Promotes LDLR Degradation. Life 2025, 15, 1321. https://doi.org/10.3390/life15081321
Yan W, Zhong Y, Fang S. A Novel Small-Molecule GRP94 Modulator Increases PCSK9 Secretion and Promotes LDLR Degradation. Life. 2025; 15(8):1321. https://doi.org/10.3390/life15081321
Chicago/Turabian StyleYan, Wenjing, Yongwang Zhong, and Shengyun Fang. 2025. "A Novel Small-Molecule GRP94 Modulator Increases PCSK9 Secretion and Promotes LDLR Degradation" Life 15, no. 8: 1321. https://doi.org/10.3390/life15081321
APA StyleYan, W., Zhong, Y., & Fang, S. (2025). A Novel Small-Molecule GRP94 Modulator Increases PCSK9 Secretion and Promotes LDLR Degradation. Life, 15(8), 1321. https://doi.org/10.3390/life15081321