Department of Integrative Biotechnology, Sungkyunkwan University, Suwon, 16419, Republic of Korea.
Exp Mol Med. 2023 Dec;55(12):2475-2497. doi: 10.1038/s12276-023-01117-7. Epub 2023 Dec 1.
Protein lysine methyltransferases (PKMTs) play crucial roles in histone and nonhistone modifications, and their dysregulation has been linked to the development and progression of cancer. While the majority of studies have focused on the oncogenic functions of PKMTs, extensive evidence has indicated that these enzymes also play roles in tumor suppression by regulating the stability of p53 and β-catenin, promoting α-tubulin-mediated genomic stability, and regulating the transcription of oncogenes and tumor suppressors. Despite their contradictory roles in tumorigenesis, many PKMTs have been identified as potential therapeutic targets for cancer treatment. However, PKMT inhibitors may have unintended negative effects depending on the specific cancer type and target enzyme. Therefore, this review aims to comprehensively summarize the tumor-suppressive effects of PKMTs and to provide new insights into the development of anticancer drugs targeting PKMTs.
蛋白赖氨酸甲基转移酶（PKMTs）在组蛋白和非组蛋白修饰中发挥着关键作用，其失调与癌症的发生和发展有关。虽然大多数研究都集中在 PKMTs 的致癌功能上，但大量证据表明，这些酶还通过调节 p53 和 β-连环蛋白的稳定性、促进 α-微管蛋白介导的基因组稳定性以及调节癌基因和肿瘤抑制基因的转录来发挥肿瘤抑制作用。尽管它们在肿瘤发生中的作用相互矛盾，但许多 PKMTs 已被确定为癌症治疗的潜在治疗靶点。然而，PKMT 抑制剂可能会因特定的癌症类型和靶酶而产生意想不到的负面影响。因此，本综述旨在全面总结 PKMT 的肿瘤抑制作用，并为开发针对 PKMT 的抗癌药物提供新的思路。
