Background: Nox4 is known to be regulated primarily at the transcriptional level and regulates myofibroblast differentiation. Results: Nox4 protein expression is suppressed by Hic-5 via Cbl-c-and HSP27-mediated ubiquitination and proteasomal degradation. Conclusion: Nox4 is posttranslationally regulated by Hic-5, and its interacting proteins, Cbl-c and HSP27 regulate myofibroblast differentiation and senescence. Significance: Prosenescence and profibrotic effects of Nox4 may be mitigated by Hic-5-mediated suppression of its protein expression.
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