We have studied a role of GAPDH in neuronal cell death, especially focusing on the protein binding of GAPDH with an E3 ligase Siah as the key component of the death signaling. The existence of a novel GAPDH binding protein, Associated Molecule of GAPDH (AMG) was previously reported by our group which exists in several isoforms including 62kDa and 50kDa proteins (Cascio et al, SFN abstract 2004). Results of in vitro binding experiments indicate that the binding of AMG and GAPDH is increased upon treatment of GAPDH with nitric oxide (NO) generators, such as SNP or GSNO. Further in vitro binding studies were performed to explore the function of AMG which revealed inhibition of the GAPDH/Siah binding in the presence of AMG. These effects are being confirmed in cellular systems. Additionally, both AMG over-expression and AMG RNAi treatment lead to morphological changes in several cell types, though it is still unclear if these changes are directly associated with GAPDH. AMG may act to inhibit the recently descr...