近日，武汉大学中南医院刘胡丹研究小组发现，Aurora B激酶直接磷酸化并稳定MYC来促进T细胞白血病的发生。相关论文2020年2月10日发表于国际学术期刊《癌细胞》。

Author: Jue Jiang, Jingchao Wang, Ming Yue, Xiaolian Cai, Tianci Wang, Chao Wu, Hexiu Su, Yanwu Wang, Meng Han, Yingchi Zhang, Xiaofan Zhu, Peng Jiang, Peng Li, Yonghua Sun, Wuhan Xiao, Hui Feng, Guoliang Qing, Hudan Liu

Issue&Volume: 2020/02/10

Abstract: Deregulation of MYC plays an essential role in T cell acute lymphoblastic leukemia(T-ALL), yet the mechanisms underlying its deregulation remain elusive. Herein, weidentify a molecular mechanism responsible for reciprocal activation between AuroraB kinase (AURKB) and MYC. AURKB directly phosphorylates MYC at serine 67, counteractingGSK3β-directed threonine 58 phosphorylation and subsequent FBXW7-mediated proteasomaldegradation. Stabilized MYC, in concert with T cell acute lymphoblastic leukemia 1(TAL1), directly activates AURKB transcription, constituting a positive feedforward loop that reinforces MYC-regulatedoncogenic programs. Therefore, inhibitors of AURKB induce prominent MYC degradationconcomitant with robust leukemia cell death. These findings reveal an AURKB-MYC regulatorycircuit that underlies T cell leukemogenesis, and provide a rationale for therapeutictargeting of oncogenic MYC via AURKB inhibition.

DOI: 10.1016/j.ccell.2020.01.001

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(20)30040-4