The E3 ligase SMURF1 stabilizes p27 via UbcH7 catalyzed K29-linked ubiquitin chains to promote cell migration SMURF1-UbcH7 K29 ubiquitination of p27 and cell migration.

Ubiquitination is a key regulator of protein stability and function. The multifunctional protein p27 is known to be degraded by the proteasome following K48-linked ubiquitination. However, we recently reported that when the ubiquitin-conjugating enzyme UbcH7 (UBE2L3) is overexpressed, p27 is stabilized, and cell cycle is arrested in multiple diverse cell types including eye lens, retina, HEK-293, and HELA cells.

Redox Regulation in Age-Related Cataracts: Roles for Glutathione, Vitamin C, and the NRF2 Signaling Pathway.

Age is the biggest risk factor for cataracts, and aberrant oxidative modifications are correlated with age-related cataracts, suggesting that proper redox regulation is important for lens clarity. The lens has very high levels of antioxidants, including ascorbate and glutathione that aid in keeping the lens clear, at least in young animals and humans. We summarize current functional and genetic data supporting the hypothesis that impaired regulation of oxidative stress leads to redox dysregulation and cataract.

Proteostasis in aging-associated ocular disease.

Vision impairment has devastating consequences for the quality of human life. The cells and tissues associated with the visual process must function throughout one's life span and maintain homeostasis despite exposure to a variety of insults. Maintenance of the proteome is termed proteostasis, and is vital for normal cellular functions, especially at an advanced age.

Dietary Patterns, Carbohydrates, and Age-Related Eye Diseases.

Over a third of older adults in the U.S. experience significant vision loss, which decreases independence and is a biomarker of decreased health span.

Regulation of clathrin-mediated endocytosis by dynamic ubiquitination and deubiquitination.

Background: Clathrin-mediated endocytosis in budding yeast requires the regulated recruitment and disassociation of more than 60 proteins at discrete plasma membrane punctae. Posttranslational modifications such as ubiquitination may play important regulatory roles in this highly processive and ordered process. However, although ubiquitination plays an important role in cargo selection, functions for ubiquitination of the endocytic machinery are not known.

Analysis of yeast endocytic site formation and maturation through a regulatory transition point.

The earliest stages of endocytic site formation and the regulation of endocytic site maturation are not well understood. Here we analyzed the order in which the earliest proteins are detectable at endocytic sites in budding yeast and found that an uncharacterized protein, Pal1p/Ydr348cp, is also present at the initial stages of endocytosis. Because Ede1p (homologue of Eps15) and clathrin are the early-arriving proteins most important for cargo uptake, their roles during the early stages of endocytosis were examined more comprehensively.

Clathrin-mediated endocytosis in budding yeast.

Clathrin-mediated endocytosis in the budding yeast Saccharomyces cerevisiae involves the ordered recruitment, activity and disassembly of nearly 60 proteins at distinct sites on the plasma membrane. Two-color live-cell fluorescence microscopy has proven to be invaluable for in vivo analysis of endocytic proteins: identifying new components, determining the order of protein arrival and dissociation, and revealing even very subtle mutant phenotypes. Yeast genetics and functional genomics facilitate identification of complex interaction networks between endocytic proteins and their regulators.