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. 2015 May 13;5:10066. doi: 10.1038/srep10066

Figure 8. A proposed mechanism underlying the regulation of Sox4 expression and HBV replication.

Figure 8

Sox4 expression is tightly controlled by HBV at multiple levels. HBV stimulates YY1 expression through the MAPK signaling, and YY1 subsequently enhances Sox4 promoter activity to activate Sox4 transcription. miR-335, miR-129-2 and miR-203 down-regulate Sox4 mRNA, whereas HBV suppresses the microRNAs expression via epigenetic modification to up-regulate Sox4 post-transcriptionally. Sox4 protein is degraded by polyubiquitin-dependent proteasome, while HBsAg protects Sox4 from degradation by interacting directly with Sox4, leading to up-regulating Sox4 post-translationally. Moreover, HBV-activated Sox4 facilitates the viral replication by binding directly to the viral genomic DNA via its HMG domain. Thus, HBV replication and Sox4 expression are highly correlated and tightly controlled by a positive feedback mechanism.