Roles of N-Myc and STAT interactor in cancer: From initiation to dissemination

Pruitt, Hawley C.; Devine, Daniel J.; Samant, Rajeev S.

identified as yet another NMI binding partner. 3 SOX10 is a member of the Sox family of transcription factors that are evolutionarily conserved and classified by their HMG box, which contains a DNA binding and bending domain. SOX proteins are essential for embryonic development and control many cell fate decisions, including programming of embryonic stem cells. 60 SOX10 is well-known for its role in neural crest development during embryogenesis. 61 The SOX10 protein contains a nuclear localization signal and a nuclear export sequence, allowing it to shuttle in and out of the nucleus. 62 NMI and SOX10 co-localized in the nucleus of C6 glioma cells. 3 This may explain how NMI, repeatedly observed in the cytoplasm, physically interacts with other transcription factors without a nuclear localization signal of its own. Shlierf et al. showed that NMI differentially influenced SOX10-mediated transcriptional activity in a promoter-dependent manner. NMI increased SOX10-mediated transcription of one target gene, myelin protein zero, a major structural component of peripheral myelin. However, in the same study, the activity of a second SOX10 target gene, dopachrome tautomerase promoter, was unchanged by NMI. 3 This suggests that NMI does not act as a global cofactor for SOX10-mediated transcription, and that genomic context and other factors may play a determinative role.