Cancer cells resistant to a diverse set of hydrophobic drugs are known as MDR cells (multidrug-resistant). Large membrane proteins overproduced in MDR cells, belong to a family of transport P-glycoproteins known as ATP-binding cassette transporter proteins (ABC-ATPases). These proteins were initially thought to affect the permeability of cells to drugs, but they were later found to to be pumps that remove drugs from cells at the cost of ATP hydrolysis. There are seven major families of ABC(ATP-binding cassette) proteins, two of them are shown on this pathway, MDR/TAP (Multi-Drug Resistance) and MRP (Multi-Drug Resistance Related Proteins). Members of the MDR/TAP subfamily are involved in multi-drug resistance as well as antigen presentation. Additional factors involved in detoxification are the P450 cytochromes (CYPs), glutathione-S-transferase (GST).Lack of MDR3 can cause a form of Progressive Familial Intrahepatic Cholestasis (PFIC), a heterogeneous group of autosomal recessive liver disorders, characterized by early onset of cholestasis that progresses to cirrhosis and liver failure before adulthood.
Contributor: Craig Monell Ph.D.
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