N-Myc Antibody #9405

Members of the Myc/Max/Mad network function as transcriptional regulators with roles in various aspects of cell behavior, including proliferation, differentiation, and apoptosis (1). These proteins share a common basic-helix-loop-helix leucine zipper (bHLH-ZIP) motif required for dimerization and DNA-binding. Max was originally discovered based on its ability to associate with c-Myc and found to be required for the ability of Myc to bind DNA and activate transcription (2). Subsequently, Max has been viewed as a central component of the transcriptional network, forming homodimers as well as heterodimers with other members of the Myc and Mad families (1). The association between Max and either Myc or Mad can have opposing effects on transcriptional regulation and cell behavior (1). The Mad family consists of four related proteins; Mad1, Mad2 (Mxi1), Mad3, and Mad4, and the more distantly related members of the bHLH-ZIP family, Mnt and Mga. Like Myc, the Mad proteins are tightly regulated with short half-lives. In general, Mad family members interfere with Myc-mediated processes, such as proliferation, transformation, and prevention of apoptosis by inhibiting transcription (3,4).

In humans the Myc family consists of 5 genes: c-Myc, N-Myc, L-Myc, R-Myc, and B-Myc. While c-Myc is expressed in many proliferating cells, N-Myc expression is very restricted, with highest levels in during embryonic development and then in the adult during B-cell development. These expression patterns and results from targeted deletion of N-Myc suggest that N-Myc plays an important role in tissue development and differentiation (5). In addition, amplification or overexpression of N-Myc has been found in human neuroblastomas and is associated with rapid progression and poor prognosis (6,7).