Figure 7.

Proposed Model: The figure shows that mutation in GNE inhibits sialic acid synthesis that may cause hyposialylation of IGF-1R. IGF-1R gets activated upon IGF-1 ligand binding and transduces the downstream signal to activate AKT that phosphorylate BAD leading to its dissociation from BCL2 which is anti-apoptotic signal to rescue cell cycle arrest and cell happily survives. Simultaneously, ERK may be downregulated in hyposialylated cells to cause dephosphorylation of BAD and its association with BCL2 continues to mediate mitochondrial dysfunction and cell apoptosis. A balance between cell survival and apoptosis pathway will determine the cell fate.