Role of the ubiquitin-proteasome in protein quality control and signaling: implication in the pathogenesis of eye diseases.

The ubiquitin-proteasome pathway (UPP) plays important roles in many cellular functions, such as protein quality control, cell cycle control, and signal transduction. The selective degradation of aberrant proteins by the UPP is essential for the timely removal of potential cytotoxic damaged or otherwise abnormal proteins. Conversely, accumulation of the cytotoxic abnormal proteins in eye tissues is etiologically associated with many age-related eye diseases such as retina degeneration, cataract, and certain types of glaucoma. Age- or stress-induced impairment or overburdening of the UPP appears to contribute to the accumulation of abnormal proteins in eye tissues. Cell cycle and signal transduction are regulated by the conditional UPP-dependent degradation of the regulators of these processes. Impairment or overburdening of the UPP could also result in dysregulation of cell cycle control and signal transduction. The consequences of the improper cell cycle and signal transduction include defects in ocular development, wound healing, angiogenesis, or inflammatory responses. Methods that enhance or preserve UPP function or reduce its burden may be useful strategies for preventing age-related eye diseases.