Fpr1 (FK506-sensitive proline rotamase 1), a protein of the FKBP12 (FK506-binding protein 12 kDa) family in Saccharomyces cerevisiae, is a primary target for the immunosuppressive agents FK506 and rapamycin. Fpr1 inhibits calcineurin and TORC1 (target of rapamycin complex 1) when bound to FK506 and rapamycin, respectively. Although Fpr1 is recognised to play a crucial role in the efficacy of these drugs, its physiological functions remain unclear. In a hmo1Δ (high mobility group family 1-deleted) yeast strain, deletion of FPR1 induced severe growth defects, which could be alleviated by increasing the copy number of RPL25 (ribosome protein of the large subunit 25), suggesting that RPL25 expression was affected in hmo1Δfpr1Δ cells. In the current study, extensive chromatin immunoprecipitation (ChIP) and ChIP-sequencing analyses revealed that Fpr1 associates specifically with the upstream activating sequences of nearly all RPG (ribosomal protein gene) promoters, presumably in a manner dependent on Rap1 (repressor/activator site binding protein 1). Intriguingly, Fpr1 promotes the binding of Fhl1/Ifh1 (forkhead-like 1/interacts with forkhead 1), two key regulators of RPG transcription, to certain RPG promoters independently of and/or cooperatively with Hmo1. Furthermore, mutation analyses of Fpr1 indicated that for transcriptional function on RPG promoters, Fpr1 requires its N-terminal domain and the binding surface for rapamycin, but not peptidyl-prolyl isomerase activity. Notably, Fpr1 orthologues from other species also inhibit TORC1 when bound to rapamycin, but do not regulate transcription in yeast, which suggests that these two functions of Fpr1 are independent of each other.

FPR1（˚F K506敏感p ROLINE ř otamase 1 ）中，FKBP12（的蛋白质FK 506-1 b inding p rotein 12 kDa）的家族在酿酒酵母，是用于免疫抑制剂FK506和雷帕霉素的主要目标。FPR1抑制钙调磷酸酶和TORC1（吨ARGET ö ˚F ř apamycin Ç omplex 1）当结合于FK506和雷帕霉素，分别。尽管人们公认Fpr1在这些药物的功效中起着至关重要的作用，但其生理功能仍不清楚。在一个hmo1 Δ（ħ IGH莫相容性组家庭1-删除）酵母菌株，缺失FPR1诱导严重的生长缺陷，这可通过增加的拷贝数来减轻RPL25（ř ibosome p rotein所述的升ARGE亚基25），这表明RPL25表达在受影响的hmo1 Δ FPR1 Δ细胞。在目前的研究中，广泛染色质免疫沉淀（ChIP）和芯片测序分析显示，FPR1与几乎所有RPG（的上游激活序列特异性关联ř ibosomal p rotein克的方式烯）的启动子，推测依赖的Rap1（ř epressor /一个ctivator点结合p rotein 1）。有趣的是，FPR1促进FHL1 / Ifh1（结合˚F扫ħ ead-升IKE 1 /我nteracts与˚F扫ħead 1）是RPG转录的两个关键调节因子，独立于Hmo1和/或与Hmo1协同作用于某些RPG启动子。此外，Fpr1的突变分析表明，对于RPG启动子的转录功能，Fpr1需要其N末端结构域和雷帕霉素的结合表面，但不需要肽基-脯氨酰异构酶活性。值得注意的是，来自其他物种的Fpr1直向同源物在与雷帕霉素结合时也抑制TORC1，但不调节酵母中的转录，这表明Fpr1的这两个功能彼此独立。