Proteomics analysis reveals the differential impact of the p97 inhibitor CB-5083 on protein levels in various cellular compartments of the HL-60 cell line.

Abstract

Human p97/VCP is a vital AAA ATPase (ATPase associated with diverse cellular activity) that plays critical roles in protein homeostasis by regulating autophagy, endosomal trafficking, and the ubiquitin-proteasome system. Global proteomics analysis of p97/VCP inhibition with CB-5083 has been performed in HCT116 colon cells. Here, we examined the impact of CB-5083 treatment in another cancer model, the HL-60 acute myeloid leukemia cell line, employing subcellular fractionation combined with label-free proteomics to analyze changes in protein levels across cytoplasmic, nuclear, and insoluble membrane protein compartments. The results reveal distinct compartment-specific protein regulation, providing insight into p97/VCP's cellular mechanisms and its potential for targeted therapeutic applications.