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科学研究
20200210 Direct Phosphorylation and Stabilization of MYC by Aurora B Kinase Promote T-cell Leukemogenesis
发布时间:2020-02-13  来源:  阅读次数:

Jiang, J., Wang, J., Yue, M., Cai, X., Wang, T., Wu, C., Su, H., Wang, Y., Han, M., Zhang, Y., Zhu, X.F., Jiang, P., Li, P., Sun, Y.H., Xiao, W.H., Feng, H., Qing, G.L., Liu, H.D.* (2020). Direct Phosphorylation and Stabilization of MYC by Aurora B Kinase Promote T-cell Leukemogenesis. Cancer Cell.


Abstract

Summary 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 GSK3β-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.

原文链接见:

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


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