Fig. 7
From: Hypoxia-induced Slug SUMOylation enhances lung cancer metastasis
Provisional model of Hypoxia-induced SUMOylation in cancer metastasis. 1. The SUMO-1 protein is activated by conjugation to the E1 heterodimer. 2. SUMO-1 is subsequently transferred from an E1 to the unique E2 enzyme Ubc9. 3. Ubc9–SUMO-1 and E3 (PIAS family) directly bind to chromatin-bound Slug. 4. SUMO-1 covalently conjugates to the C-terminus of Slug. 5. Slug SUMOylation increases the recruitment of corepressors, such as Sin3A, CtBP, HDAC1 and HDAC2, to its N-terminus. 6. Then, Slug represses the expression of target genes associated with the epithelial markers such as E-cadherin, occludin, claudin-1, and integrin α3 to promote cancer metastasis. 7. Hypoxia increases Slug SUMOylation by attenuating its binding to SENP1/2. In conclusion, SUMOylation further enhances Slug-mediated cancer cell migration and invasion and tumor metastasis