Regulation of MYCN. (IMAGE)
Caption
(A) Transcription factors such as E2 promoter binding factor (E2F) and specific protein 1 (SP1) can directly increase the expression of MYCN, while activating transcription factor 3 (ATF3) reduces MYCN expression. (B) Several kinases activate the transcriptional function of MYCN either by directly phosphorylating the protein or via down-regulation of an E3 ligase to affect the protein stability of MYCN. (C) Phosphorylated MYCN regulates downstream gene expression and further promotes tumorigenesis. (D) MYCN associates with the polycomb repressive complex (PRC) to suppress the expression of genes required for cell differentiation. AKT, protein kinase B; AURKA, aurora kinase A; FBXW7, F-Box and WD repeat domain containing 7; GSK-3β, glycogen synthase kinase 3 beta; MAX, Myc-associated factor X; PI3K, phosphoinositide 3-kinase; PLK1, polo-like kinase-1.
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