NMyc

N-Myc, also known as MYCN, is a member of the MYC family of transcription factors encoded by the MYCN gene on chromosome 2p24.3. It is most prominently expressed in the developing nervous system and plays a key role in regulating neural progenitor proliferation and differentiation. As a basic helix-loop-helix leucine zipper (bHLH-LZ) transcription factor, N-Myc forms heterodimers with MAX and binds to E-box DNA sequences to regulate transcription of genes involved in cell growth, metabolism, and protein synthesis.

The activity of N-Myc is tightly controlled at transcriptional and post-translational levels. Protein stability is governed by ubiquitin-proteasome pathways, and phosphorylation-dependent recognition by E3 ligases such as FBXW7 has been implicated in targeting N-Myc for degradation. Co-factors such as TRRAP link N-Myc to histone acetyltransferase–mediated regulation of chromatin and transcription.

Clinical significance: Amplification or overexpression of MYCN is a defining feature of a subset of neuroblastomas and is associated with rapid disease progression and poor prognosis. Assessment of MYCN status is standard in neuroblastoma risk stratification and informs treatment planning.

Therapeutic context: Direct pharmacologic inhibition of N-Myc is challenging due to the nature of transcription factors; however, multiple indirect strategies are under investigation. These include agents that suppress MYCN transcription, reduce N-Myc protein stability, or inhibit downstream pathways activated by N-Myc. Preclinical studies have shown activity for BET inhibitors and other approaches that indirectly reduce N-Myc signaling.

See also: MYC family, neuroblastoma, gene amplification.