Role of ubiquitin in quality control of lens proteins

Tufts University Boston, Boston MA

Investigators

Linked publications & trials

Abstract

The lens cells and their protein constituents have to remain functional for a lifetime to preserve the transparent function of the lens. Damage to lens proteins results in protein aggregation and cataract. Efficient removal and/or repair of damaged lens proteins is essential to prevent protein aggregation and cataract formation. The damage is normally prevented and repaired through the action of multiple anti-oxidant, chaperone and protein repair enzymes. Damaged proteins that are not repairable must be degraded to prevent aggregation and precipitation, a major mechanism of cataractogenesis. Our previous work demonstrated that a proteolytic system named the ubiquitinproteasome pathway plays an important role in selective removal of damaged or abnormal proteins from lens cells. To directly test the role of the ubiquitin-proteasome pathway in quality control of lens proteins, we will test whether impairment of the ubiquitin-proteasome pathway increases levels of various forms of damaged proteins in the lens and reduces lens transparency. The proposed work will increase our knowledge of how the lens maintains its transparent function and will potentially identify targets of pharmaceutical interventions for prevention or treatment of age-related cataract.