Research
| Title： | Direct Phosphorylation and Stabilization of MYC by Aurora B Kinase Promote T-cell Leukemogenesis |
|---|---|
| First author： | Jiang, Jue; Wang, Jingchao; Yue, Ming; Cai, Xiaolian; Wang, Tianci; Wu, Chao; Su, Hexiu; Wang, Yanwu; Han, Meng; Zhang, Yingchi; Zhu, Xiaofan; Jiang, Peng; Li, Peng; Sun, Yonghua; Xiao, Wuhan; Feng, Hui; Qing, Guoliang; Liu, Hudan |
| Journal： | CANCER CELL |
| Years： | 2020 |
| DOI： | 10.1016/j.ccell.2020.01.001 |
| 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, we identify a molecular mechanism responsible for reciprocal activation between Aurora B kinase (AURKB) and MYC. AURKB directly phosphorylates MYC at serine 67, counteracting GSK3b-directed threonine 58 phosphorylation and subsequent FBXW7-mediated proteasomal degradation. Stabilized MYC, in concert with T cell acute lymphoblastic leukemia 1 (TAL1), directly activates AURKB transcription, constituting a positive feedforward loop that reinforces MYC-regulated oncogenic programs. Therefore, inhibitors of AURKB induce prominent MYC degradation concomitant with robust leukemia cell death. These findings reveal an AURKB-MYC regulatory circuit that underlies T cell leukemogenesis, and provide a rationale for therapeutic targeting of oncogenic MYC via AURKB inhibition. |
