In this review, we have summarized the information from a study on FKBP12 (FK506 binding protein 12 kDa) with a view to understand its drug-free, physiological roles in transcription of ribosomal protein gene in Saccharomyces cerevisiae. FKBP12 with peptidyl-prolylisomerase (PPIase) activity is widely conserved among many eukaryotes. FKBP12 is a primary target for the two structurally related drugs, FK506 and rapamycin. FKBP12 bound with FK506 or rapamycin inhibits calcineurin and target of rapamycin complex 1 (TORC1), respectively. The molecular mechanisms of the effect of FKBP12 in the presence of these drugs have been elucidated. Conversely, the physiological role of FKBP12 has been unclear, especially in yeast. Our study revealed that the deletion of FPR1 (FK506-sensitive prolinerotamase 1 gene), which encodes yeast FKBP12, induced severe growth defect synthetically with deletion of HMO1 (high mobility group family 1). HMO1 encodes an HMGB family protein involved in transcription of ribosomal component genes. Fpr1 was shown to bind specifically to the promoters of ribosomal protein genes (RPGs) dependent on Rap1 (repressor/activator binding protein 1). Importantly, Fpr1 and Hmo1 promote the binding of Fhl1/Ifh1 (forkhead-like 1/interacts with forkhead 1), key regulators of RPG transcription, to certain RPG promoters independently and/or cooperatively with each other. Taken together, we conclude that Fpr1 physiologically functions as transcription factor of RPGs in S. cerevisiae. To our knowledge, this is the first study to demonstrate that FKBP12 participates in ribosome synthesis independently of drugs, and it may also provide a clue to the unidentified function of other PPIase proteins.

在这篇综述中，我们总结了 FKBP12（FK506 结合蛋白 12 kDa）研究的信息，以了解其在酿酒酵母核糖体蛋白基因转录中的无药物生理作用。具有肽基脯氨酰异构酶 (PPIase) 活性的 FKBP12 在许多真核生物中广泛保守。FKBP12 是两种结构相关的药物 FK506 和雷帕霉素的主要靶点。FKBP12 与 FK506 或雷帕霉素结合分别抑制钙调神经磷酸酶和雷帕霉素复合物 1 (TORC1) 的靶点。在这些药物存在下 FKBP12 作用的分子机制已经阐明。相反，FKBP12 的生理作用尚不清楚，尤其是在酵母中。我们的研究表明FPR1的缺失（FK506 敏感脯氨酸旋转酶 1 基因），编码酵母 FKBP12，通过缺失HMO1（高迁移率族 1）诱导严重的生长缺陷。HMO1编码参与核糖体成分基因转录的 HMGB 家族蛋白。Fpr1 被证明与依赖于 Rap1（阻遏物/激活剂结合蛋白 1）的核糖体蛋白基因 (RPG) 的启动子特异性结合。重要的是，Fpr1 和 Hmo1 促进 Fhl1/Ifh1（类叉头 1/与叉头 1 相互作用）（RPG 转录的关键调节因子）与某些 RPG 启动子独立和/或相互协作地结合。综上所述，我们得出结论，Fpr1 在生理学上作为酿酒酵母中 RPG 的转录因子起作用. 据我们所知，这是第一项证明 FKBP12 独立于药物参与核糖体合成的研究，它也可能为其他 PPIase 蛋白的未知功能提供线索。