Rbbp6-KO Mouse

Rbbp6, short for Retinoblastoma binding protein 6, is a cancer-related protein with E3 ubiquitin ligase activity. It is involved in regulating the cell cycle, apoptosis, and pre-mRNA 3' end processing. Rbbp6 has multiple isoforms, with isoform 1 interacting with tumor suppressors p53 and pRB, and regulating p53 through its ubiquitin ligase activity [2].

In glioblastoma, CRISPR/Cas9 knockout screens revealed Rbbp6 as essential for glioblastoma stem cell (GSC) maintenance. Targeting Rbbp6 inhibited GSC proliferation and tumor initiation. Mechanistically, it mediates K63-linked ubiquitination of CPSF3, regulating alternative polyadenylation, and ultimately maintaining high MYC expression in GSCs [1].

In diabetic kidney disease, Rbbp6 promotes the degradation of ERRα through K48-linked polyubiquitination, contributing to mitochondrial injury in proximal renal tubular cells. Conditional ERRα overexpression or RbbP6 inhibition reduced mitochondrial damage in diabetic mice [3].

In summary, Rbbp6 plays crucial roles in multiple biological processes and disease conditions. Gene knockout-based research, such as in glioblastoma and diabetic kidney disease models, has revealed its importance in maintaining cancer stem cells and contributing to mitochondrial injury, respectively. This provides potential therapeutic targets for these diseases.