Direct Phosphorylation and Stabilization of MYC by Aurora B Kinase Promote T Cell Leukemogenesis

The significance of MYC deregulation has been well-documented in T-cell acute lymphoblastic leukemia (T-ALL). MYC acts as an oncogenic driver in T-ALL and particularly in maintaining leukemia-initiating cell activity. Protein interactome analysis identified Aurora B kinase (AURKB) as a specific MYC binding partner and depletion of AURKB reduced the steady-state levels of MYC. Mechanistic studies demonstrated that AURKB directly phosphorylated MYC and promoted MYC protein stability, and conversely AURKB deficiency elicited rapid MYC degradation. We thus predicted that abrogation of AURKB would affect global MYC transcriptional program. To assess the transcriptional change in response to AURKB knockdown, RNA-Seq was performed using AURKB or control-depleted CUTLL1 cells. Overall design: CUTLL1 cells were infected with lentiviruses expressing shRNA targeting AURKB or control and cultured for 48 h. Total RNAs from three biological replicates were extracted for sequencing analysis.