N-myc proto-oncogene protein also known as N-Myc or basic helix-loop-helix protein 37 (bHLHe37), is a protein that in humans is encoded by the MYCN gene.
N-myc proto-oncogene protein also known as N-Myc or basic helix-loop-helix protein 37 (bHLHe37), is a protein that in humans is encoded by the MYCN gene.
The MYCN gene is a member of the MYC family of 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. [5] N-Myc is highly expressed in the fetal brain and is critical for normal brain development. [6]
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. [7] N-Myc and MYCNOS are co-regulated both in normal development and in tumor cells, so it is possible that the two transcripts are functionally related. [8] It has been shown that the antisense RNA encodes for a protein, named NCYM, 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. [9]
Amplification and overexpression of N-Myc can lead to tumorigenesis. Excess N-Myc is associated with a variety of tumors, most notably neuroblastomas where patients with amplification of the N-Myc gene tend to have poor outcomes. [10] [11] [12] MYCN can also be activated in neuroblastoma and other cancers through somatic mutation. [13] Intriguingly, recent genome-wide H3K27ac profiling in patient-derived NB samples revealed four distinct SE-driven epigenetic subtypes, characterized by their own and specific master regulatory networks. Three of them are named after the known clinical groups: MYCN-amplified, MYCN non-amplified high-risk, and MYCN non-amplified low-risk NBs, while the fourth displays cellular features which resemble multipotent Schwann cell precursors. Interestingly, the cyclin gene CCND1 was regulated through distinct and shared SEs in the different subtypes, and, more importantly, some tumors showed signals belonging to multiple epigenetic signatures, suggesting that the epigenetic landscape is likely to contribute to intratumoral heterogeneity. [14]
N-Myc has been shown to interact with MAX. [15] [16]
N-Myc is also stabilized by aurora A which protects it from degradation. [17] Drugs that target this interaction are under development, and are designed to change the conformation of aurora A. Conformational change in Aurora A leads to release of N-Myc, which is then degraded in a ubiquitin-dependent manner. [18]
Being independent from MYCN/MAX interaction, MYCN is also a transcriptional co-regulator of p53 in MYCN-amplified neuroblastoma.[ citation needed ] MYCN alters transcription of p53 target genes which regulate apoptosis responses and DNA damage repair in cell cycle. This MYCN-p53 interaction is through exclusive binding of MYCN to C-terminal domains of tetrameric p53. As a post-translational modification, MYCN binding to C-terminal domains of tetrameric p53 impacts p53 promoter selectivity and interferes other cofactors binding to this region. [19]
An oncogene is a gene that has the potential to cause cancer. In tumor cells, these genes are often mutated, or expressed at high levels.
p53, also known as Tumor protein P53, cellular tumor antigen p53, or transformation-related protein 53 (TRP53) is a regulatory protein that is often mutated in human cancers. The p53 proteins are crucial in vertebrates, where they prevent cancer formation. As such, p53 has been described as "the guardian of the genome" because of its role in conserving stability by preventing genome mutation. Hence TP53 is classified as a tumor suppressor gene.
Heterogeneous nuclear ribonucleoproteins (hnRNPs) are complexes of RNA and protein present in the cell nucleus during gene transcription and subsequent post-transcriptional modification of the newly synthesized RNA (pre-mRNA). The presence of the proteins bound to a pre-mRNA molecule serves as a signal that the pre-mRNA is not yet fully processed and therefore not ready for export to the cytoplasm. Since most mature RNA is exported from the nucleus relatively quickly, most RNA-binding protein in the nucleus exist as heterogeneous ribonucleoprotein particles. After splicing has occurred, the proteins remain bound to spliced introns and target them for degradation.
Aurora kinase A also known as serine/threonine-protein kinase 6 is an enzyme that in humans is encoded by the AURKA gene.
Myc is a family of regulator genes and proto-oncogenes that code for transcription factors. The Myc family consists of three related human genes: c-myc (MYC), l-myc (MYCL), and n-myc (MYCN). c-myc was the first gene to be discovered in this family, due to homology with the viral gene v-myc.
Phorbol-12-myristate-13-acetate-induced protein 1 is a protein that in humans is encoded by the PMAIP1 gene, and is also known as Noxa.
MYC proto-oncogene, bHLH transcription factor is a protein that in humans is encoded by the MYC gene which is a member of the myc family of transcription factors. The protein contains basic helix-loop-helix (bHLH) structural motif.
Transcription factor E2F1 is a protein that in humans is encoded by the E2F1 gene.
MAX is a gene that in humans encodes the MAX transcription factor.
DNA-binding protein inhibitor ID-3 is a protein that in humans is encoded by the ID3 gene.
PITSLRE serine/threonine-protein kinase CDC2L1 is an enzyme that in humans is encoded by the CDK11B gene.
L-myc-1 proto-oncogene protein is a protein that in humans is encoded by the MYCL1 gene.
N-myc-interactor also known as N-myc and STAT interactor is a protein that in humans is encoded by the NMI gene.
ATP-dependent RNA helicase DDX1 is an enzyme that in humans is encoded by the DDX1 gene.
40S ribosomal protein S7 is a protein that in humans is encoded by the RPS7 gene.
MNT is a Max-binding protein that is encoded by the MNT gene
40S ribosomal protein S8 is a protein that in humans is encoded by the RPS8 gene.
Aflatoxin B1 aldehyde reductase member 2 is an enzyme that in humans is encoded by the AKR7A2 gene.
Pvt1 oncogene, also known as PVT1 or Plasmacytoma Variant Translocation 1 is a long non-coding RNA gene. In mice, this gene was identified as a breakpoint site in chromosome 6;15 translocations. These translocations are associated with murine plasmacytomas. The equivalent translocation in humans is t(2;8), which is associated with a rare variant of Burkitt's lymphoma. In rats, this breakpoint was shown to be a common site of proviral integration in retrovirally induced T lymphomas. Transcription of PVT1 is regulated by Myc.
WRAP53 is a gene implicated in cancer development. The name was coined in 2009 to describe the dual role of this gene, encoding both an antisense RNA that regulates the p53 tumor suppressor and a protein involved in DNA repair, telomere elongation and maintenance of nuclear organelles Cajal bodies.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.