Protein ubiquitin is an immunophilin.
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.
Davis
Diane L
DL
Health Sciences Department, Salisbury University, Salisbury, Maryland, USA.
Soldin
Steven J
SJ
D006801:Humans; D020104:Immunophilins / Q000378:metabolism*; D007376:Interleukin-2 / Q000378:metabolism; D019169:Jurkat Cells; D008970:Molecular Weight; D011485:Protein Binding; D015398:Signal Transduction / Q000502:physiology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013601:T-Lymphocytes / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism*; D014461:Ultracentrifugation
D007376:Interleukin-2; D025801:Ubiquitin; D020104:Immunophilins