Cross-talk between redox regulation and the ubiquitin–proteasome system in mammalian cell differentiation

• Redox signaling is a fundamental regulation of cell fate upon differentiation.
• UPS plays important role in the maintenance of pluripotency and the triggering of differentiation.
• UPS regulates through degradation the redox-mediated effectors of differentiation.
• Interactome network of cardiomyocytes differentiated from ESC highlighted UPS role in pluripotency.
• UPS likewise genome stability were found essential in the maintenance of pluripotency state.

BackgroundEmbryogenesis and stem cell differentiation are complex and orchestrated signaling processes. Reactive oxygen species (ROS) act as essential signal transducers in cellular differentiation, as has been shown through recent discoveries. On the other hand, the ubiquitin–proteasome system (UPS) has long been known to play an important role in all cellular regulated processes, including differentiation.Scope of reviewIn the present review, we focus on findings that highlight the interplay between redox signaling and the UPS regarding cell differentiation. Through systems biology analyses, we highlight major routes during cardiomyocyte differentiation based on redox signaling and UPS modulation.Major conclusionOxygen availability and redox signaling are fundamental regulators of cell fate upon differentiation. The UPS plays an important role in the maintenance of pluripotency and the triggering of differentiation.General significanceCellular differentiation has been a matter of intense investigation mainly because of its potential therapeutic applications. Understanding regulatory mechanisms underlying cell differentiation is an important issue. Correspondingly, the role of UPS and regulation of redox processes have been emerged as essential factors to control the fate of cells upon differentiation. This article is part of a Special Issue entitled Redox regulation of differentiation and de-differentiation.