AIMP2-DX2 Research Program

Aminoacyl-tRNA synthetase-interacting multi-functional proteins (AIMPs) are scaffolding proteins for the assembly of the macromolecular tRNA synthetase complex. Among the 3 types of AIMPs, AIMP2 (also known as p38) possesses anti-proliferative and cell death-promoting activity through multiple pathways such as tumor-derived growth factor (TGF)-β, p53, HSP70, KRAS, tumor necrosis factor (TNF)-α signaling and Wnt signaling.

A variant of AIMP2 in which exon 2 is deleted by alternative splicing, AIMP2-DX2, has been detected in cancer cell lines and tissues. AIMP2-DX2 competes with AIMP2 for the binding to target proteins, consequently inhibiting the tumor suppressive activity of AIMP2. Increased ratio of AIMP2-DX2 versus AIMP2 showed positive correlation to poor clinical outcome of lung cancer, as well as chemoresistance of ovarian cancer.  

The research compound BC-DX101has been shown to suppressed the AIMP2-DX2 mRNA transcript, leading to the inhibition of the AIMP2-DX2 activity and tumor suppression. Taken together, these data suggest that AIMP2-DX2 is an attractive candidate for cancer diagnosis and therapy.  Researchers at Biocon have developed unique assays to assess the interactions of AIMP2DX2 with KRAS and HSP70 and have shown the following effects: 

• AIMP2-DX2 is oncogenic
• AIMP2-DX2 occurs in cancer patients (and has genetic correlation so that patients can be identified)
• AIMP2-DX2 can be directly detected in vitro and in vivo  
• AIMP2-DX2 can be knocked down chemically in vitro
• AIMP2-DX2 inhibitors slow tumor regression
• Knock-down of AIMP-DX2 can be detected biochemically and correlated with disease regression