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. 2021 Mar 10;12(3):395. doi: 10.3390/genes12030395

Figure 4.

Figure 4

DDX11-mediated regulation of EZH2-p21 and PI3K/AKT/mTOR signaling pathways in HCC cells. The E2F1 factor promotes transcription of the genes coding for DDX11 and the Enhancer of zeste homolog 2 (EZH2), the subunit with methyl-transferase activity of the polycomb repressive complex 2 (PRC2). DDX11 has been proposed to activate the PI3K/AKT/mTOR signaling pathway and stabilize EZH2 by preventing its proteolytic degradation (question marks indicate that the underlying molecular mechanisms have not been elucidated). In turn, stabilized EZH2 cooperates with E2F1 to activate DDX11 gene transcription forming a positive feedback loop that leads to cell proliferation. Besides, inhibition of p21 gene transcription by EZH2 also contributes to cell growth.