THE DRUG RESISTANCE-RELATED PROTEIN LRP IS THE HUMAN MAJOR VAULT PROTEIN

Multidrug-resistant cancer cells frequently overexpress the 110-kD LRP protein (originally named Lung Resistance-related Protein). LRP overe xpression has been found to predict a poor response to chemotherapy in acute myeloid leukaemia and ovarian carcinoma. We describe the clonin g and chromosome localization of the gene coding for this novel protei n. The deduced LRP amino acid sequence shows 87.7% identity with the 1 04-kD rat major vault protein Vault's are multi-subunit structures tha t may be involved in nucleo-cytoplasmic transport. The LRP gene is loc ated on chromosome 16, close to the genes coding for multidrug resista nce-associated protein and protein kinase C-beta, and may mediate drug resistance, perhaps via a transport process.