Proteomics

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Differential Impact of p97 Inhibitor CB-5083 on Protein Dynamics in Nucleus, Cytoplasm, and Membrane Compartments

ABSTRACT: Human p97/VCP is a vital AAA ATPase (ATPase associated with diverse cellular activity) plays critical roles in autophagy, endosomal trafficking, and the ubiquitin-proteasome system. Mutations in p97 cause inclusion body myopathy associated with paget’s disease of bone and frontotemporal dementia. P97 is overexpressed in several cancers. The selective active site inhibitor CB-5083 targets p97’s D2 domain and shows potential as an anti-cancer therapeutic, though it has faced clinical setbacks due to off-target effects. To investigate the protein levels changed of HL60 cells (acute myeloid leukemia cell line) by CB-5083 in cytoplasmic, nuclear, and insoluble membrane compartments, we employed fractionation and label-free proteomic analysis. Results reveal distinct compartment-specific protein regulation, providing insight into CB5083’s cellular mechanisms and potential for more targeted therapeutic applications.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Ting-Yu Wang  

LAB HEAD: Tsui-Fen Chou

PROVIDER: PXD056029 | Pride | 2025-05-07

REPOSITORIES: Pride

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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.

Huang Wenxuan W   Qiu Yanping Y   Huynh Diana D   Wang Ting-Yu TY   Chou Tsui-Fen TF  

microPublication biology 20241127

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-  ...[more]

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