RBX1/ROC1-SCF E3 ubiquitin ligase is required for mouse embryogenesis and cancer cell survival

Abstract

RBX1 (also known as ROC1) is a RING subunit of SCF (Skp1, Cullins, F-box proteins) E3 ubiquitin ligases, required for SCF to direct a timely degradation of diverse substrates, thereby regulating numerous cellular processes under both physiological and pathological conditions. Previous studies have shown that RBX1 is essential for growth in yeast, Caenorhabditis elegans and Drosophila. The role of RBX1 in mouse development and in regulation of cancer cell survival was unknown. Our recent work demonstrated that RBX1 is an essential gene for mouse embryogenesis, and targeted disruption of RBX1 causes embryonic lethality at E7.5 due to hypoproliferation as a result of p27 accumulation. We also showed that RBX1 is overexpressed in a number of human cancers, and siRNA silencing of RBX1 caused cancer cell death as a result of sequential induction of G2-M arrest, senescence and apoptosis. These findings reveal a physiological role of RBX1 during mouse development and a pathological role for the survival of human cancer cells. Differential outcomes between normal (growth arrest) and cancer cells (cell death) upon RBX1 disruption/silencing suggest RBX1 as a valid anticancer target. © 2009 Jia and Sun; licensee BioMed Central Ltd.