Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80131 Naples, Italy.
Department of Sciences and Technologies, University of Sannio, 82100 Benevento, Italy.
Molecules. 2021 Oct 18;26(20):6296. doi: 10.3390/molecules26206296.
The transcription factor ZNF224 is a Kruppel-like zinc finger protein that consists of 707 amino acids and contains 19 tandemly repeated CH zinc finger domains that mediate DNA binding and protein-protein interactions. ZNF224 was originally identified as a transcriptional repressor of genes involved in energy metabolism, and it was demonstrated that ZNF224-mediated transcriptional repression needs the interaction of its KRAB repressor domain with the co-repressor KAP1 and its zinc finger domains 1-3 with the arginine methyltransferase PRMT5. Furthermore, the protein ZNF255 was identified as an alternative isoform of ZNF224 that possesses different domain compositions mediating distinctive functional interactions. Subsequent studies showed that ZNF224 is a multifunctional protein able to exert different transcriptional activities depending on the cell context and the variety of its molecular partners. Indeed, it has been shown that ZNF224 can act as a repressor, an activator and a cofactor for other DNA-binding transcription factors in different human cancers. Here, we provide a brief overview of the current knowledge on the multifaceted interactions of ZNF224 and the resulting different roles of this protein in various cellular contexts.
锌指蛋白 224（ZNF224）是一种转录因子，由 707 个氨基酸组成，包含 19 个串联重复的 CH 锌指结构域，介导 DNA 结合和蛋白质-蛋白质相互作用。ZNF224 最初被鉴定为参与能量代谢的基因的转录抑制剂，研究表明 ZNF224 介导的转录抑制需要其 KRAB 抑制结构域与共抑制因子 KAP1 相互作用，以及其锌指结构域 1-3 与精氨酸甲基转移酶 PRMT5 相互作用。此外，还鉴定出 ZNF255 是 ZNF224 的一种替代异构体，具有不同的结构域组成，介导独特的功能相互作用。随后的研究表明，ZNF224 是一种多功能蛋白，能够根据细胞环境和其各种分子伴侣的不同，发挥不同的转录活性。事实上，已经表明 ZNF224 可以在不同的人类癌症中作为其他 DNA 结合转录因子的抑制剂、激活剂和共因子发挥作用。在这里，我们简要概述了 ZNF224 多方面相互作用的最新知识，以及该蛋白在各种细胞环境中产生的不同作用。
