Branching Out: Improved Signaling by Heterotypic Ubiquitin Chains

Ubiquitin chains of distinct topologies control the stability, interactions, or localization of many proteins in eukaryotic cells, and thus play an essential role in cellular information transfer. It has recently been found that ubiquitin chains can be combined to produce branched conjugates that are characterized by the presence of at least two linkages within the same polymer. Akin to their homotypic counterparts, branched chains elicit a wide array of biological outputs, further expanding the versatility, specificity, and efficiency of ubiquitin-dependent signaling. This review discusses emerging understanding of the synthesis and function of branched ubiquitin chains.