Publications by authors named "Hiroaki Iio"
Targeted protein degradation is a groundbreaking modality in drug discovery; however, the regulatory mechanisms are still not fully understood. Here, we identify cellular signaling pathways that modulate the targeted degradation of the anticancer target BRD4 and related neosubstrates BRD2/3 and CDK9 induced by CRL2- or CRL4 -based PROTACs. The chemicals identified as degradation enhancers include inhibitors of cellular signaling pathways such as poly-ADP ribosylation (PARG inhibitor PDD00017273), unfolded protein response (PERK inhibitor GSK2606414), and protein stabilization (HSP90 inhibitor luminespib).
View Article and Find Full Text PDFArticle Synopsis
- * Researchers discovered that senescent cells form unique nuclear structures called senescence-associated nuclear proteasome foci (SANPs) that require both ubiquitination and proteasome activity to form.
- * Reducing RAD23B, a protein involved in SANP formation, boosts mitochondrial activity and increases reactive oxygen species levels without changing other signs of senescence, highlighting SANPs' significance in aging cells.