Lingering mysteries of ubiquitin-chain assembly

The small protein ubiquitin is often linked to substrates as a polymer. Such polymers vary in both linkage and length, which has important consequences for their function. Surprisingly, the mechanisms of ubiquitin-chain assembly are still not known. Deciphering them will shed light on why substrates differ in the extent and timing of polyubiquitin modification and how ancillary ubiquitination factors function.