As spatial proximity of E2s to substrates is important for ubiquitin transfer and ubiquitin chain elongation [25, 26], the binding of ATF3 directly to the MDM2 RING domain raises an intriguing possibility that ATF3 might compete with p53 for MDM2-mediated ubiquitination thereby activating the tumor suppressor. This evidence concerns the gene TP53 and neoplasm.