IDENTIFICATION OF TOR INTERACTING PROTEINS

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。我们正在研究Tor信号级联，它感知营养并调节基因表达、翻译和核糖体的生物发生，从酵母到人类已经保守了10亿年。Tor蛋白是一种新的蛋白激酶，其功能被免疫抑制的抗真菌药物雷帕霉素与Prolyl异构酶FKBP12结合而抑制。我们专注于抗增殖药物雷帕霉素，它通过阻断激活T淋巴细胞所需的信号事件来抑制免疫系统。雷帕霉素用于治疗和预防器官移植受者的移植排斥反应。雷帕霉素是土壤细菌的产物，在自然界中可能扮演着与免疫抑制不同的角色，可能是作为一种毒素来抑制竞争微生物的生长。基于这一假设，我们详细分析了雷帕霉素在酿酒酵母中的作用机制。我们希望与酵母资源中心合作，继续对TOR蛋白进行分析。

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.