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. 2023 Oct 27;12(2):101156. doi: 10.1016/j.gendis.2023.101156

Figure 3.

Figure 3

Feedback regulation of MYCN. 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, stabilizes, and enhances 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.