Mechanisms of generating polyubiquitin chains of different topology

Randy Suryadinata; Siti Nur Ain Roesley; George Yang; Boris Sarčević

doi:10.3390/cells3030674

Mechanisms of generating polyubiquitin chains of different topology

Cells. 2014 Jul 1;3(3):674-89. doi: 10.3390/cells3030674.

Authors

Randy Suryadinata¹, Siti Nur Ain Roesley², George Yang², Boris Sarčević³

Affiliations

¹ CSIRO Materials Science and Engineering, Parkville, Victoria 3052, Australia.
² Cell Cycle and Cancer Unit, St. Vincent's Institute of Medical Research, Fitzroy, Victoria 3065, Australia.
³ Cell Cycle and Cancer Unit, St. Vincent's Institute of Medical Research, Fitzroy, Victoria 3065, Australia. bsarcevic@svi.edu.au.

Abstract

Ubiquitination is an important post-translational process involving attachment of the ubiquitin molecule to lysine residue/s on a substrate protein or on another ubiquitin molecule, leading to the formation of protein mono-, multi- or polyubiquitination. Protein ubiquitination requires a cascade of three enzymes, where the interplay between different ubiquitin-conjugating and ubiquitin-ligase enzymes generates diverse ubiquitinated proteins topologies. Structurally diverse ubiquitin conjugates are recognized by specific proteins with ubiquitin-binding domains (UBDs) to target the substrate proteins of different pathways. The mechanism/s for generating the different ubiquitinated proteins topologies is not well understood. Here, we will discuss our current understanding of the mechanisms underpinning the generation of mono- or polyubiquitinated substrates. In addition, we will discuss how linkage-specific polyubiquitin chains through lysines-11, -48 or -63 are formed to target proteins to different fates by binding specific UBD proteins.