PUBLICATION
Direct Phosphorylation and Stabilization of MYC by Aurora B Kinase Promote T-cell Leukemogenesis
- Authors
- Jiang, J., Wang, J., Yue, M., Cai, X., Wang, T., Wu, C., Su, H., Wang, Y., Han, M., Zhang, Y., Zhu, X., Jiang, P., Li, P., Sun, Y., Xiao, W., Feng, H., Qing, G., Liu, H.
- ID
- ZDB-PUB-200213-8
- Date
- 2020
- Source
- Cancer Cell 37: 200-215.e5 (Journal)
- Registered Authors
- Liu, Hudan, Wu, Chao
- Keywords
- Aurora B kinase, FBXW7, MYC, T-ALL, patient-derived xenograft, phosphorylation, protein stability, zebrafish T-ALL model
- MeSH Terms
-
- Animals
- Aurora Kinase A/genetics
- Aurora Kinase A/immunology
- Aurora Kinase B/immunology
- Aurora Kinase B/metabolism*
- Cell Line, Tumor
- F-Box-WD Repeat-Containing Protein 7/immunology
- Humans
- Mice
- Phosphorylation
- Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy
- Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/immunology*
- Protein Kinase Inhibitors/pharmacology
- T-Lymphocytes/drug effects
- T-Lymphocytes/immunology*
- Transcriptional Activation/drug effects
- Transcriptional Activation/immunology
- Zebrafish
- PubMed
- 32049046 Full text @ Cancer Cell
Citation
Jiang, J., Wang, J., Yue, M., Cai, X., Wang, T., Wu, C., Su, H., Wang, Y., Han, M., Zhang, Y., Zhu, X., Jiang, P., Li, P., Sun, Y., Xiao, W., Feng, H., Qing, G., Liu, H. (2020) Direct Phosphorylation and Stabilization of MYC by Aurora B Kinase Promote T-cell Leukemogenesis. Cancer Cell. 37:200-215.e5.
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 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping