title: 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.
authors.affiliation: Health Sciences Department, Salisbury University, Salisbury, Maryland, USA.
authors.forename: Diane L
authors.initials: DL
authors.lastname: Davis
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Soldin
mesh_terms: 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
chemical_list: D007376:Interleukin-2; D025801:Ubiquitin; D020104:Immunophilins