Physiological Overview of the Potential Link between the UPS and Ca²⁺ 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. Ca²⁺ 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 Ca²⁺ signaling remains unclear. In the present review, we describe the relationship between the UPS and Ca²⁺ signaling, including Ca²⁺-associated proteins, to understand the end point of oxidative stress. The UPS modulates Ca²⁺ signaling via the degradation of Ca²⁺-related proteins, including Ca²⁺ channels and transporters. Conversely, the modulation of UPS is driven by increases in the intracellular Ca²⁺ concentration. The multifaceted relationship between the UPS and Ca²⁺ plays critical roles in different tissue systems. Thus, we highlight the potential crosstalk between the UPS and Ca²⁺ signaling by providing an overview of the UPS in different organ systems and illuminating the relationship between the UPS and autophagy.