NAE1 and colorectal cancer: In colorectal cancer, the levels of NEDD8, NAE1 and UBE2M are all remarkably elevated in colorectal cancer tissues, as compared to matched adjacent normal tissues.46 Notably, a C2-WW-HECT ligase, Smurf1, is positively correlated with NEDD8, NAE1 and UBE2M.