Chemical and genetic strategies for manipulating polyubiquitin chain structure.

Ubiquitin can be conjugated to lysine residues of other ubiquitin molecules to form polymers called polyubiquitin chains. Ubiquitin has seven lysine residues, creating the potential for seven distinct types of chains, at least five of which have been observed in vitro or in vivo. A subset of these chains mediates substrate targeting to proteasomes, whereas other types of chains have been implicated in nonproteolytic signaling pathways. In this chapter, we outline chemical and genetic strategies that can be used to deduce (or control) the structures of polyubiquitin chains in vitro and in living cells.