N-Myc

N-myc proto-oncogene protein also known as N-Myc or basic helix-loop-helix protein 37 (bHLHe37), is a is_associated_with::protein that in humans is encoded by the MYCN is_associated_with::gene.

Function
The MYCN gene is a member of the MYC family of is_associated_with::transcription factors and encodes a protein with a basic helix-loop-helix (bHLH) domain. This protein is located in the cell nucleus and must dimerize with another bHLH protein in order to bind DNA. N-Myc is highly expressed in the fetal brain and is critical for normal brain development.

The MYCN gene has an antisense RNA, N-cym or MYCNOS, transcribed from the opposite strand which can be translated to form a protein product. N-Myc and MYCNOS are co-regulated both in normal development and in tumor cells, so it is possible that the two proteins are functionally related. It has been shown that NCYM antisense RNA encodes for a protein that has originated de novo and is specific to human and chimpanzee. This NCYM protein inhibits GSK3b and thus prevents MYCN degradation. Transgenic mice that harbor human MYCN/NCYM pair often show neuroblastomas with distant metastasis, which are atypical for normal mice. Thus NCYM represents a rare example of a de novo gene that has acquired molecular function and plays a major role in oncogenesis.

Clinical significance
Amplification and overexpression of N-Myc can lead to tumorigenesis. Excess N-Myc is associated with a variety of tumors, most notably is_associated_with::neuroblastomas where patients with amplification of the N-Myc gene tend to have poor outcomes.

Interactions
N-Myc has been shown to interact with MAX.

N-Myc is also stabilized by is_associated_with::aurora A which protects it from degradation. Drugs that target this interaction are under development, and are designed to change the conformation of is_associated_with::aurora A. Conformational change in is_associated_with::Aurora A leads to release of N-Myc, which is then degraded in a is_associated_with::ubiquitin-dependent manner.