RNA‐binding motif protein 39 (RBM39): An emerging cancer target
| Autor: | Yuewei Xu, Hector C. Keun, Anke Nijhuis |
|---|---|
| Přispěvatelé: | Astra Zeneca Pharmaceuticals, Imperial College Healthcare NHS Trust- BRC Funding |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Spliceosome Tumour regression RNA splicing Cancer therapy RBM39 Computational biology Biology indisulam PROTAC 03 medical and health sciences 0302 clinical medicine molecular glues Neoplasms Gene expression Humans Pharmacology & Pharmacy Pharmacology Sulfonamides aryl sulphonamides Alternative splicing RNA-Binding Proteins Ubiquitin ligase Alternative Splicing 030104 developmental biology RNA-Binding Motif RNA-Binding Motifs biology.protein 1115 Pharmacology and Pharmaceutical Sciences DCAF15 030217 neurology & neurosurgery |
| Zdroj: | British Journal of Pharmacology. 179:2795-2812 |
| ISSN: | 1476-5381 0007-1188 |
| Popis: | RNA-binding motif protein 39 (RBM39) is an RNA-binding protein involved in transcriptional co-regulation and alternative RNA splicing. Recent studies have revealed that RBM39 is the unexpected target of aryl sulphonamides, which act as molecular glues between RBM39 and the DCAF15-associated E3 ubiquitin ligase complex leading to selective degradation of the target. Loss of RBM39 leads to aberrant splicing events and differential gene expression, thereby inhibiting cell cycle progression and causing tumour regression in a number of preclinical models. Many clinical studies have shown that aryl sulphonamides were well tolerated, but their clinical performance was limited due to an insufficient understanding of the target, RBM39 biology and a lack of predictive biomarkers. This review summarises the current knowledge of RBM39 function and discusses the therapeutic potential of this spliceosome target in cancer therapy. LINKED ARTICLES: This article is part of a themed issue on New avenues in cancer prevention and treatment (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.12/issuetoc. |
| Databáze: | OpenAIRE |
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