Proteasome maturation protein (POMP) (POMP)

Proteasome maturation protein (POMP) is an essential molecular chaperone required for the biogenesis of the 20S proteasome core particle (UniProt Q9Y244). It functions by coordinating the assembly of the proteasome's alpha and beta subunits and facilitating the dimerization of two precursor half-proteasomes (PubMed: 10523314). In oncological contexts, such as multiple myeloma and colorectal cancer, POMP is frequently overexpressed to support the high proteasomal demand of rapidly dividing cells, making its mRNA a target for knockdown strategies (PubMed: 26416143). Experimental approaches using siRNA or antisense oligonucleotides against POMP mRNA have demonstrated the ability to induce proteotoxic stress and sensitize malignant cells to existing proteasome inhibitors like bortezomib (PubMed: 21832174). However, germline mutations or deficiency in POMP are associated with severe autoinflammatory disorders, including KLICK syndrome and Proteasome-associated autoinflammatory syndrome (PRAAS), due to impaired protein degradation and subsequent immune activation (PubMed: 27018445). Targeting the mRNA of POMP represents a potential therapeutic avenue to bypass resistance mechanisms in protein-degradation-dependent cancers.

Other names

hUMP1UMP1PNAS-110Proteasome maturation protein mRNA

RNA interference or antisense-mediated degradation of POMP mRNA to inhibit the assembly of the 20S proteasome, leading to proteotoxic stress and apoptosis.