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
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/immunology*
  • Aurora Kinase B/immunology
  • Aurora Kinase B/metabolism*
  • Cell Line, Tumor
  • Phosphorylation
  • T-Lymphocytes/drug effects
  • T-Lymphocytes/immunology*
  • Mice
  • Animals
  • Zebrafish
  • F-Box-WD Repeat-Containing Protein 7/immunology
  • Transcriptional Activation/drug effects
  • Transcriptional Activation/immunology
  • Humans
  • Protein Kinase Inhibitors/pharmacology
  • Aurora Kinase A/genetics
  • Aurora Kinase A/immunology
(all 18)
PubMed
32049046 Full text @ Cancer Cell
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
Figures
No images available
Expression
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
whu201TgTransgenic Insertion
    whu202TgTransgenic Insertion
      zdf7TgTransgenic Insertion
        zdf13TgTransgenic Insertion
          1 - 4 of 4
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          Human Disease / Model
          No data available
          Sequence Targeting Reagents
          Fish
          Antibodies
          Orthology
          Engineered Foreign Genes
          Marker Marker Type Name
          CreEFGCre
          DsRed2EFGDsRed2
          EGFPEFGEGFP
          mCherryEFGmCherry
          1 - 4 of 4
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          Mapping
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          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.