Department of Veterinary Biochemistry, Yamaguchi University, Yamaguchi, Japan.
Cancer Sci. 2023 Jul;114(7):2729-2738. doi: 10.1111/cas.15811. Epub 2023 Apr 27.
FK506 binding protein 52 (FKBP52) (gene name FKBP4) is a 52 kDa protein that belongs to the FKBP family; it binds to the immunosuppressant FK506 and has proline isomerase activity. In addition to its FK domain-containing peptidylprolyl isomerase activity, FKBP52 also acts as a cochaperone through the tetratricopeptide repeat domain that mediates binding to heat shock protein 90. Previous studies have reported that FKBP52 is associated with hormone-dependent, stress-related, and neurodegenerative diseases, revealing its diverse functions. In particular, the effects of FKBP52 on cancer have attracted considerable attention. FKBP52 promotes the growth of hormone-dependent cancers by activating steroid hormone receptors. Recent studies have shown that the expression of FKBP52 is increased not only in steroid hormone-dependent cancer cells but also in colorectal, lung, and liver cancers, revealing its diverse functions that contribute to cancer growth. This review summarizes reports related to hormone-dependent cancer and cell proliferation in terms of the structure of FKBP52 and its function on interacting molecules.
FK506 结合蛋白 52(FKBP52)(基因名称 FKBP4)是一种 52kDa 的蛋白质,属于 FKBP 家族;它与免疫抑制剂 FK506 结合,并具有脯氨酰肽基顺反异构酶活性。除了其 FK 结构域包含的肽基脯氨酰顺反异构酶活性外,FKBP52 还通过四肽重复结构域作为共伴侣发挥作用,该结构域介导与热休克蛋白 90 的结合。先前的研究报告表明,FKBP52 与激素依赖性、应激相关和神经退行性疾病有关,揭示了其多样化的功能。特别是,FKBP52 对癌症的影响引起了相当大的关注。FKBP52 通过激活甾体激素受体促进激素依赖性癌症的生长。最近的研究表明,FKBP52 的表达不仅在甾体激素依赖性癌细胞中增加,而且在结直肠癌、肺癌和肝癌中也增加,揭示了其促进癌症生长的多样化功能。本综述总结了 FKBP52 的结构及其与相互作用分子相互作用的功能方面与激素依赖性癌症和细胞增殖相关的报告。