IDENTIFICATION OF TOR INTERACTING PROTEINS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We are studying the Tor signaling cascade, which senses nutrients and regulates gene expression, translation, and ribosome biogenesis and has been conserved over a billion years of evolution from yeast to humans. The Tor proteins are novel protein kinases whose functions are inhibited by the immunosuppressive antifungal drug rapamycin in complex with the prolyl isomerase FKBP12. We focus on the antiproliferative drug rapamycin, which suppresses the immune system by blocking signaling events required for activation of T-lymphocytes. Rapamycin is used to treat and prevent graft rejection in organ transplant recipients. Rapamycin is a product of a soil bacterium and likely plays a role in nature distinct from immunosuppression, possibly as a toxin to inhibit growth of competing microorganisms. Based on this hypothesis, we have analyzed in detail the mechanisms of rapamycin action in the yeast Saccharomyces cerevisiae. We would like to continue our analysis of the TOR proteins in collaboration with the Yeast Resource Center.