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Assuring a healthy proteome is indispensable for survival and organismal health. Proteome disbalance and the loss of the proteostasis buffer are hallmarks of various diseases. The essential molecular chaperone Hsp90 is a regulator of the heat shock response via HSF1 and a stabilizer of a plethora of signaling proteins. In this review, we summarize the role of Hsp90 in the cellular and organismal regulation of proteome maintenance.
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http://dx.doi.org/10.3390/cells11162479 | DOI Listing |
Drug Resist Updat
March 2025
School of Pharmacy, Fujian Medical University, Fuzhou 350122, China; Fujian Provincial Key Laboratory of Natural Medicine Pharmacology, Fujian Medical University, Fuzhou 350122, China. Electronic address:
Aims: TRAP1 is involved in metabolic reprogramming and promotes drug resistance. We aimed to explore whether a novel HSP90 inhibitor, C210, overcomes doxorubicin (DOX) resistance of quiescent breast cancer cells by targeting TRAP1.
Methods: Breast cancer cells were induced to quiescence by hypoxia and low glucose.
Am J Cancer Res
February 2025
Department of Clinical Oncology, Queen Elizabeth Hospital Hong Kong SAR, China.
Nasopharyngeal carcinoma (NPC) initially responds well to platinum-based therapy but often develops resistance. Combining therapies may offer a viable approach to address this resistance. Heat shock protein 90 (Hsp90) has shown promising anticancer activity in various cancer types.
View Article and Find Full Text PDFOncoimmunology
December 2025
Department of Hematology and Medical Oncology, Emory University, Atlanta, GA, USA.
We conducted a phase Ib/II clinical trial to evaluate the safety, feasibility, and clinical activity of combining pembrolizumab (anti-PD-1) with XL888 (Hsp90 inhibitor) in patients with advanced colorectal cancer (CRC). We hypothesized that this regimen would modulate soluble and cellular immune mediators and enhance clinical outcomes. The trial employed a 3 + 3 open-label design, with an expansion cohort at the recommended phase II dose (RP2D) in treatment-refractory, mismatch repair-proficient CRC patients.
View Article and Find Full Text PDFCell Death Dis
March 2025
Department of Biomedical Sciences, University of Padova, Padova, Italy.
The mitochondrial chaperone TRAP1 is a key regulator of cellular homeostasis and its activity has important implications in neurodegeneration, ischemia and cancer. Recent evidence has indicated that TRAP1 mutations are involved in several disorders, even though the structural basis for the impact of point mutations on TRAP1 functions has never been studied. By exploiting a modular structure-based framework and molecular dynamics simulations, we investigated the effect of five TRAP1 mutations on its structure and stability.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
March 2025
Department of Hepatobiliary and Pancreatic Surgery and Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China.
Chronic infections with hepatitis E virus (HEV), especially those of genotype 3 (G3), frequently lead to liver fibrosis and cirrhosis in patients. However, the causation and mechanism of liver fibrosis triggered by chronic HEV infection remain poorly understood. Here, we found that the viral multiple-domain replicase (ORF1) undergoes unique ubiquitin-proteasomal processing leading to formation of the EV-erived MAD ctivator (HDSA), a viral polypeptide lacking putative helicase and RNA polymerase domains.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!