Fig. 2
From: Aspartate β-hydroxylase as a target for cancer therapy
Regulation of ASPH expression and ASPH involvement in signaling pathways. The expression of the ASPH protein can be regulated at several levels. The ASPH gene can be amplified in tumor cells and its transcription activated by IN/IGF-1 and Wnt/ β-catenin pathways or induced by hypoxia. At the posttranscriptional level, miR-200a and miR-135a can downregulate ASPH expression. Stability of the ASPH protein can be reduced by phosphorylation with GSK-3β. Conversely, ASPH can enhance GSK-3β activity by inhibition of its phosphorylation with AKT and p38 kinases. ASPH also supports cell proliferation, epithelial-mesenchymal transition, migration, invasion, and angiogenesis and consequently tumor growth and metastasis by hydroxylation of the Notch receptor and ligands (ex. JAG) and interaction with pRb, vimentin and ADAMs. Finally, inactivation of NK cells by ASPH has been demonstrated. Green arrow, activation signal; red bar, inhibitory signal