Myc proto-oncogene protein at the MYC:Aurora kinase A interface (MYC:AURKA interface)

The MYC:Aurora kinase A (AURKA) protein-protein interface is a significant therapeutic target because it regulates the stability of the MYC oncoprotein (Dauch et al., Cancer Cell, 2016). MYC is a master transcription factor that drives cell growth and proliferation but is notoriously difficult to target directly with small molecules due to its lack of a traditional binding pocket (UniProt P01106). Aurora A kinase interacts with the N-terminus of MYC, specifically protecting it from degradation by the E3 ubiquitin ligase FBXW7 (Brockmann et al., Cancer Cell, 2013). This interaction is non-catalytic, meaning it depends on the physical conformation of Aurora A rather than its kinase activity (Gustafson et al., Cancer Cell, 2014). In many cancers, such as neuroblastoma and hepatocellular carcinoma, this stabilization leads to pathologically high levels of MYC. Therapeutic strategies involve using conformation-disrupting inhibitors that change the shape of Aurora A, thereby breaking the complex and triggering MYC degradation. Drugs like Alisertib and CD532 have demonstrated the ability to reduce MYC levels through this mechanism in preclinical models. Targeting this interface provides a unique opportunity to indirectly inhibit MYC, which is otherwise considered an undruggable target.

Other names

c-Myc:Aurora A complexMYC:AURKA PPIMYCN:AURKA interfaceAurora A-MYC interactionMYC-AURKA protein-protein interface

Disruption of the protein-protein interaction between MYC and Aurora A, leading to the loss of MYC stabilization and subsequent proteasomal degradation.