NPM1 has been defined as an autoantigen in systemic lupus erythematosus, scleroderma, and hepatocellular Tetrabenazine carcinoma. Structurally, NPM1 belongs to the nucleoplasmin family of proteins, and forms pentamers in a ring-like configuration. In NLP family members, pentamer formation requires a highly similar amino-terminal region, known as the core oligomerization domain. The available Xray crystal models of NPM1, like those for other NLP members, do not contain the carboxyl-terminal domains. In previous studies, Ulanet et al. showed that NPM1 was not only overexpressed in HCC tissue when compared with non-malignant liver cells, but also had several distinct biochemical properties. When compared with surrounding cirrhotic tissue of the same specimen and normal non-cirrhotic livers, NPM1 in tumor tissue had increased mobility by sodium dodecyl sulfate polyacrylamide gel electrophoresis, and also exhibited an additional form, consistent with a high molecular weight, SDS-stable oligomeric complex. Furthermore, NPM1 in HCC cells was more Bazedoxifene Acetate sensitive to granzyme B cleavage, a property enriched among human autoantigens as compared with non-antigen proteins. In attempting to determine the biochemical basis for these observed differences, Ulanet et al. found that a construct modeling alternative initiation at the seventh methionine, M7-NPM, had identical features to the tumor form of NPM1 described above. Interestingly, since our initial studies, alternative initiation of translation at the fifth and ninth methionines in mouse and human NPM1 have been identified by other groups, using high resolution ribosome profiling and amino-terminal peptide proteomics. Although initiation at the seventh methionine was not found in these studies, it remains possible that M7-NPM may occur in specific cell types not included in the above experiments, including pre-cancerous or malignant cells. Additionally, M7-NPM may share similar biochemical and structural properties with constructs lacking the first four or eight amino-terminal residues, as would occur with translational initiation at the fifth or ninth methionines, respectively.