RNA-binding motif protein 39 (RBM39): An emerging cancer target

Yuewei Xu, Anke Nijhuis*, Hector C. Keun*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

34 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2795-2812
Number of pages18
JournalBritish Journal of Pharmacology
Volume179
Issue number12
DOIs
Publication statusPublished - Jun 2022
Externally publishedYes

Keywords

  • aryl sulphonamides
  • DCAF15
  • indisulam
  • molecular glues
  • PROTAC
  • RBM39
  • RNA splicing

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