MYC:Aurora kinase A protein-protein interaction interface (MYC:AURKA PPI)

The MYC:Aurora kinase A (AURKA) protein-protein interaction interface is a critical regulatory node in many aggressive cancers. Aurora kinase A physically interacts with MYC family proteins, particularly N-MYC, to protect them from FBXW7-mediated proteolytic degradation (Brockmann et al., 2013). This stabilization leads to the accumulation of MYC, a potent transcription factor that drives cell proliferation and survival but is traditionally considered "undruggable" (Dauch et al., 2016). By targeting the interface or inducing conformational changes in Aurora A that prevent binding, researchers can effectively trigger the rapid degradation of MYC. This strategy has shown promise in treating MYCN-amplified neuroblastoma and other MYC-driven malignancies (Gustafson et al., 2014). Small molecule inhibitors like Alisertib and the tool compound CD532 have demonstrated the ability to disrupt this complex by binding to the ATP-binding pocket of Aurora A and altering its surface topology, offering a workaround to direct MYC inhibition (Beltran et al., 2019). This approach represents a paradigm shift in targeting transcription factors by focusing on their stabilizing partners rather than the proteins themselves.

Other names

N-MYC:Aurora A complexc-MYC:Aurora A interactionAURKA:MYC interfaceMYC-AURKA complex

Allosteric modulation of Aurora kinase A to disrupt its physical association with MYC proteins, thereby promoting FBXW7-mediated MYC ubiquitination and subsequent proteasomal degradation (Gustafson et al., 2014).