Stapling proteins in the RELA complex inhibits TNFα-induced nuclear translocation of RELA. Issue 1 (1st November 2021)

• Record Type: Journal Article
• Authors: Kour, Smit; Rana, Sandeep; Kizhake, Smitha; Lagundžin, Dragana; Klinkebiel, David; Mallareddy, Jayapal Reddy; Huxford, Tom; Woods, Nicholas T.; Natarajan, Amarnath
• Is Part Of: RSC chemical biology. Volume 3:Issue 1(2022)
• Page Start: 32
• Page End: 36
• Publication Date: 2021-11-01
• Subjects: 572
• DOI: 10.1039/d1cb00183c
• Languages: English
• ISSNs: 2633-0679

Abstract

Abstract : Discovery of a spirocyclic dimer (SpiD7) that covalently modifies RELA to generate stable high molecular weight complexes. SpiD7 inhibits TNFα-induced nuclear translocation of RELA resulting in the blockade of NF-kB gene transcription, through a previously unexplored modality. Abstract : Tumor necrosis factor (TNF) α-induced nuclear translocation of the NF-κB subunit RELA has been implicated in several pathological conditions. Here we report the discovery of a spirocyclic dimer (SpiD7) that covalently modifies RELA to inhibit TNFα-induced nuclear translocation. This is a previously unexplored strategy to inhibit TNFα-induced NF-κB activation.