Physiological Overview of the Potential Link between the UPS and Ca(2+) Signaling

The ubiquitin–proteasome system (UPS) is the main proteolytic pathway by which damaged target proteins are degraded after ubiquitination and the recruit of ubiquitinated proteins, thus regulating diverse physiological functions and the maintenance in various tissues and cells. Ca(2+) signaling is raised by oxidative or ER stress. Although the basic function of the UPS has been extensively elucidated and has been continued to define its mechanism, the precise relationship between the UPS and Ca(2+) signaling remains unclear. In the present review, we describe the relationship between the UPS and Ca(2+) signaling, including Ca(2+)-associated proteins, to understand the end point of oxidative stress. The UPS modulates Ca(2+) signaling via the degradation of Ca(2+)-related proteins, including Ca(2+) channels and transporters. Conversely, the modulation of UPS is driven by increases in the intracellular Ca(2+) concentration. The multifaceted relationship between the UPS and Ca(2+) plays critical roles in different tissue systems. Thus, we highlight the potential crosstalk between the UPS and Ca(2+) signaling by providing an overview of the UPS in different organ systems and illuminating the relationship between the UPS and autophagy.