Protein ubiquitin is an immunophilin.

Abstract

The intracellular class of proteins that bind the interleukin-2 suppressing drugs (cyclosporin, tacrolimus, and sirolimus) are called immunophilins. It is believed that the drugs do not act directly on T cells to cause immunosuppression. Instead, there is evidence that drug-immunophilin complexes are responsible for the therapeutic effect. In this work, evidence is presented that ubiquitin is an immunophilin. Ubiquitin is a highly conserved protein essential to an important pathway that targets proteins for proteolysis. The interaction of these drugs could cause accelerated proteolysis of a key protein for T-cell upregulation or could cause the inhibition of proteolysis of a T-cell suppressor. It was also shown that when ubiquitin is complexed with tacrolimus, the complex inhibits calcineurin phosphatase, and it is known that immunosuppression with these drugs occurs concurrently with a decrease in the activity of this enzyme. The discovery of ubiquitin as an immunophilin has opened many new avenues to explore in relation to the effects of these drugs.