Unanchored Ubiquitin Chains, Revisited

Abstract

The small modifier protein, ubiquitin, holds a special place in eukaryotic biology because of its myriad post-translational effects that control normal cellular processes and are implicated in various diseases. By being covalently conjugated onto other proteins, ubiquitin changes their interaction landscape-fostering new interactions as well as inhibiting others-and ultimately deciding the fate of its substrates and controlling pathways that span most cell physiology. Ubiquitin can be attached onto other proteins as a monomer or as a poly-ubiquitin chain of diverse structural topologies. Among the types of poly-ubiquitin species generated are ones detached from another substrate-comprising solely ubiquitin as their constituent-referred to as unanchored, or free chains. Considered to be toxic byproducts, these species have recently emerged to have specific physiological functions in immune pathways and during cell stress. Free chains also do not appear to be detrimental to multi-cellular organisms; they can be active members of the ubiquitination process, rather than corollary species awaiting disassembly into mono-ubiquitin. Here, we summarize past and recent studies on unanchored ubiquitin chains, paying special attention to their emerging roles as second messengers in several signaling pathways. These investigations paint complex and flexible outcomes for free ubiquitin chains, and present a revised model of unanchored poly-ubiquitin biology that is in need of additional investigation.

Novel pathomechanism for spontaneous bacterial peritonitis: disruption of cell junctions by cellular and bacterial proteases

“…Inhibition of the proteasome has been validated as an important strategy in anticancer therapy. [45][46][47][48][49] We suggest that proteasome inhibition may offer a novel option to prevent degradation of occludin and to restore intestinal barrier function.…”

Conformational Space Sampled by Domain Reorientation of Linear Diubiquitin Reflected in Its Binding Mode for Target Proteins

“…In fact, the binding of linear polyubiquitin to its partner usually does not rely on the substrate; rather, the chain itself is recognized. Furthermore, unanchored linear polyubiquitins also play a role in NF‐kB signaling [40] . Thus, the results obtained for linear Ub 2 would provide relevant insights into the properties of linear polyubiquitin in vivo.…”

“…Furthermore, unanchored linear polyubiquitins also play a role in NF-kB signaling. [40] Thus, the results obtained for linear Ub 2 would provide relevant insights into the properties of linear polyubiquitin in vivo.…”

Molecular Mechanisms Underlying the Inhibition of Proliferation and Differentiation by Florfenicol in P19 Stem Cells: Transcriptome Analysis

“…KEGG pathway analysis further reveals that the upregulated module genes were significantly enriched in ubiquitin-mediated proteolysis ( Table 1 ), which indicates the involvement of ubiquitination in FLO-treated P19SCs. Ubiquitination is a posttranslational modification of proteins and participates in the selective degradation of most proteins to regulate transcription, signal transduction, cell-cycle control, and stem cell biology ( Blount et al, 2020 ). Pluripotent cells commonly utilize ubiquitin-dependent proteolysis to regulate the levels of transcription factors related to pluripotency or specify a particular differentiation route.…”