Ubiquitin is a small, 76-amino acid polypeptide that can be covalently attached to other proteins to regulate their activities. The role of ubiquitin in tagging proteins for proteasome-mediated degradation is its most well-known function, but ubiquitin regulates non-proteolytic processes as well. Ubiquitin’s versatility is due, in part, by its ability to be linked into different types of polymers, depending on which of its seven lysine connect the individual ubiquitin subunits together. Polymers assembled through ubiquitin’s lysine 48 are generally considered to be the primary “flag” targeting substrates to the proteasome for degradation. Although ubiquitin can be recognized by the proteasome directly, there is abundant evidence indicating certain ubiquitinated substrates requiring a “shuttle” protein to deliver them to the proteasome. For example, in yeast, the cyclin-dependent kinase inhibitor Far1 is only efficiently degraded by the proteasome in cells expressing a wild-type version of a shuttle protein called Rad23. We are performing an in vivo experiment to test the hypothesis that Lys48-linked polyubiquitin is, indeed, the primary degradation in cells. By switching the ubiquitin polymer-binding selectivity of Rad23 from Lys48-selective to Lys63-selective, we will determine whether Far1 is still efficiently degraded in these cells.

Effect of Rad 23 selectivity to polyubiquitin chain linkage on Far-1 degradation in yeast

253rd National Meeting (2017)

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