Polyubiquitin chains linked through the Lys48 residue of ubiquitin are most commonly associated with proteins targeted for proteosomal degradation. In contrast, polyubiquitin chains linked through the Lys63 residue of ubiquitin (Ub) are associated with nonproteolytic functions such as signal transduction. Lys63-linked polyUb chains connect components of NFκB signaling in a highly regulated manner, and genetic evidence indicates the involvement of Lys63-linked Ub chains in stress response and DNA repair. Research in yeast has suggested Lys63-linked Ub chains stimulate endocytosis.
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