Feedback regulation of MYCN. (IMAGE)
Caption
MYCN and its target genes form several feedback loops, playing important roles in regulating MYCN expression and function in tumorigenesis. (A) Pleiomorphic adenoma gene-like 2 (PLAGL2) is a transcription factor that directly activates the transcription of MYCN. MYCN can also activate PLAGL2 expression, forming a positive feedback loop. (B) MYCN upregulates p53, which leads to increased mouse double minute 2 (MDM2) expression and MDM2 binds to the mRNA of MYCN, stabilizing it and enhancing its translation. (C) Ubiquitin-specific peptidase 5 (USP5) is a deubiquitinase that specifically deubiquitinates and stabilizes MYCN, forming a positive feedback loop. (D) Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase that functions as an upstream signaling molecule to regulate MYCN expression. MYCN can also promote ALK expression, forming a positive feedback loop. (E) Aldehyde dehydrogenase 18 family member A1 (ALDH18A1) decreases the miRNA expression of both specific protein 1 (SP1) and MYCN, forming a negative feedback loop. These feedback loops highlight the complex and dynamic regulation of MYCN expression and activity in cancer cells. ERK5, extracellular signal-regulated protein kinase 5.
Credit
The authors
Usage Restrictions
Credit must be given to the creator. Only noncommercial uses of the work are permitted. No derivatives or adaptations of the work are permitted.
License
CC BY-NC-ND