Zheng Youwei, Li Xinchao, Kuang Lirun, Wang Yong
Department of General Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang, China.
Front Pharmacol. 2022 Oct 28;13:1014508. doi: 10.3389/fphar.2022.1014508. eCollection 2022.
As a member of the death-associated protein kinase (DAPK) family, DAP kinase-associated apoptosis-inducing kinase 2 (DRAK2) performs apoptosis-related functions. Compelling evidence suggests that DRAK2 is involved in regulating the activation of T lymphocytes as well as pancreatic β-cell apoptosis in type I diabetes. In addition, DRAK2 has been shown to be involved in the development of related tumor and non-tumor diseases through a variety of mechanisms, including exacerbation of alcoholic fatty liver disease (NAFLD) through SRSF6-associated RNA selective splicing mechanism, regulation of chronic lymphocytic leukemia and acute myeloid leukemia, and progression of colorectal cancer. This review focuses on the structure, function, and upstream pathways of DRAK2 and discusses the potential and challenges associated with the clinical application of DRAK2-based small-molecule inhibitors, with the aim of advancing DRAK2 research.
作为死亡相关蛋白激酶(DAPK)家族的一员,DAP激酶相关凋亡诱导激酶2(DRAK2)发挥与凋亡相关的功能。有力证据表明,DRAK2参与调节T淋巴细胞的激活以及I型糖尿病中胰腺β细胞的凋亡。此外,DRAK2已被证明通过多种机制参与相关肿瘤和非肿瘤疾病的发生发展,包括通过SRSF6相关的RNA选择性剪接机制加重酒精性脂肪性肝病(NAFLD)、调节慢性淋巴细胞白血病和急性髓系白血病以及促进结直肠癌进展。本综述聚焦于DRAK2的结构、功能和上游通路,并讨论基于DRAK2的小分子抑制剂临床应用的潜力和挑战,旨在推动DRAK2的研究。