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

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

N-myc and STAT Interactor, NMI, is one such protein that has been realized as one of the proteins that indirectly influence specific transcriptional events. The NMI gene resides on chromosome 2q23. In humans, NMI protein expression has been detected in all fetal tissues except the brain, and its expression is highest in the adult spleen, liver and kidneys. 1 The human NMI gene can code for two distinct mature mRNA transcripts that are translated identically into NMI protein products. The NMI protein is typically localized to the cytoplasm, but it has also been detected in the nucleus by multiple investigators. 2, 3 As its name reveals, NMI was first identified as a binding protein partner of oncogenic transcription factors, N-myc and c-Myc. 1 The synopsis of published literature about NMI indicates that this 38 kDa protein may function as an adapter molecule, capable of different functions depending on cellular context and proteins with which it interacts. The first one hundred amino acids of NMI comprise a coiled-coil domain that is homologous to the C. elegans protein, CEF59. The second domain consisting of the next one hundred amino acids is referred to as the NMI/IFP35 (NID) domain, due to its homology with IFP35 (interferon inducible protein 35) . All predicted domains of NMI are reported to be involved in protein-protein interactions (Fig. 1a) . Several proteins confirmed to interact with NMI are transcription factors that influence (positively or negatively) tumor progression. The studies that substantiate these important protein-protein interactions also support the proposition that NMI may have an important role in cancer (Fig. 1b) .