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Development of a versatile system for evaluating the target protein degradation activity of novel ubiquitin ligases utilizing existing PROTACs.
Biochem Biophys Res Commun
January 2025
Department of Pharmacology and Therapeutic Innovation, Nagasaki University Graduate School of Biomedical Sciences, 1-14 Bunkyo-machi, Nagasaki, 852-8521, Japan. Electronic address:
Proteolysis-Targeting Chimeras (PROTAC) are a bifunctional molecule that binds to a protein of interest (POI) and a ubiquitin ligase, thereby inducing the ubiquitination and degradation of POI. Many PROTACs currently utilize a limited number of ubiquitin ligases, such as von Hippel-Lindau (VHL) and Cereblon. Because these ubiquitin ligases are widely expressed in normal tissues, unexpected side effects can occur.
View Article and Find Full Text PDFHypoxia-Inducible Factor in Renal Cell Carcinoma: From Molecular Insights to Targeted Therapies.
Genes (Basel)
December 2024
Department of Health Science, University of Florence, 50134 Florence, Italy.
Mutations of the von Hippel-Lindau () tumor suppressor gene occur frequently in clear cell renal cell carcinoma (RCC), the predominant histology of kidney cancer, and have been associated with its pathogenesis and progression. Alterations of lead to impaired degradation of hypoxia-inducible factor 1α (HIF1α) and HIF2α promoting neoangiogenesis, which is pivotal for cancer growth. As such, targeting the VHL-HIF axis holds relevant potential for therapeutic purposes.
View Article and Find Full Text PDFRelationship between ZHX2 Expression and VHL Gene Alteration in VHL-associated and Sporadic Hemangioblastomas of the Central Nervous System.
J Kidney Cancer VHL
December 2024
Department of Urology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Central nervous system hemangioblastoma (CNS-HB) is the most common manifestation of von Hippel-Lindau disease (VHL). The main axis of the CNS-HB pathway is the VHL-HIF signaling pathway. Recently, we proposed an alternative VHL-JAK-STAT pathway in CNS-HB.
View Article and Find Full Text PDFLong-term surgical outcomes and prognosis of cervical spinal hemangioblastomas.
Clin Neurol Neurosurg
January 2025
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Fengtai District, Beijing 100070, China.
Purpose: Hemangioblastomas (HBs) occurring in the cervical spinal region are infrequently reported. Surgical resection of cervical HBs poses a significant challenge, and the long-term therapeutic outcomes remain unclear.
Methods: A comprehensive retrospective analysis was conducted to review the treatment outcomes of patients with cervical HBs from 2011 to 2021.
A patent review of von Hippel-Lindau (vhl)-recruiting chemical matter: E3 ligase ligands for PROTACs and targeted protein degradation (2019-present).
Expert Opin Ther Pat
January 2025
Centre for Targeted Protein Degradation, School of Life Sciences, University of Dundee, Dundee, UK.
Introduction: The von Hippel-Lindau (VHL) E3 ubiquitin ligase has seen extensive research due to its involvement in the ubiquitin proteasome system and role as a tumor suppressor within the hypoxia signaling pathway. VHL has become an attractive target for proteolysis targeting chimeras (PROTACs), bifunctional molecules that can induce degradation of neo-substrate proteins. The development of VHL inhibitors and PROTACs has seen rapid development since disclosure of the first non-peptidic VHL ligand (2012).
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