MYCN

MYCN is a gene that encodes the N-Myc transcription factor, a member of the MYC family. The human MYCN gene is located on chromosome 2p24–25. The N-Myc protein contains a basic helix-loop-helix leucine zipper (bHLH-LZ) domain that enables DNA binding and dimerization with MAX.

As a transcription factor, N-Myc forms heterodimers with MAX and binds to E-box DNA sequences in target promoters to regulate transcription. It influences genes involved in cell growth, metabolism, ribosome biogenesis, and differentiation, and it is particularly important for neural progenitor proliferation during brain development. In model organisms, N-Myc is essential for normal development, with loss leading to developmental defects.

Expression of N-Myc is tightly regulated at transcriptional and post-translational levels. The ubiquitin–proteasome system governs its stability, and aberrant accumulation of N-Myc can drive unchecked cell proliferation and tumorigenesis.

The best characterized clinical role of MYCN is in neuroblastoma, where gene amplification occurs in a substantial subset of cases and is strongly associated with high-risk disease and poor prognosis. MYCN status is used for risk stratification and treatment decisions. Therapeutic approaches are under investigation to lower N-Myc levels or disrupt N-Myc/MAX activity, including strategies targeting transcriptional regulation and protein stability; no approved therapies specifically targeting MYCN exist at this time.

Alterations of MYCN have also been reported in other cancers and can be associated with aggressive tumor behavior, reflecting a broader role for N-Myc in cancer biology.