1. A ubiquitin shuttle DC-UbP/UBTD2 reconciles protein ubiquitination and deubiquitination via linking UbE1 and USP5 enzymes.
- Author
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Song AX, Yang H, Gao YG, Zhou CJ, Zhang YH, and Hu HY
- Subjects
- Binding Sites, Endopeptidases genetics, Escherichia coli genetics, Escherichia coli metabolism, HEK293 Cells, Humans, Models, Molecular, Protein Binding, Protein Structure, Tertiary, RNA, Small Interfering genetics, RNA, Small Interfering metabolism, Recombinant Proteins genetics, Recombinant Proteins metabolism, Ubiquitin genetics, Ubiquitin-Activating Enzymes genetics, Ubiquitin-Specific Proteases genetics, Ubiquitin-Specific Proteases metabolism, Ubiquitination, Ubiquitins antagonists & inhibitors, Ubiquitins genetics, Endopeptidases metabolism, Protein Processing, Post-Translational, Ubiquitin metabolism, Ubiquitin-Activating Enzymes metabolism, Ubiquitins metabolism
- Abstract
The ubiquitination levels of protein substrates in eukaryotic cells are delicately orchestrated by various protein cofactors and enzymes. Dendritic cell-derived ubiquitin (Ub)-like protein (DC-UbP), also named as Ub domain-containing protein 2 (UBTD2), is a potential Ub shuttle protein comprised of a Ub-like (UbL) domain and a Ub-binding domain (UBD), but its biological function remains largely unknown. We identified two Ub-related enzymes, the deubiquitinating enzyme USP5 and the Ub-activating enzyme UbE1, as interacting partners of DC-UbP from HEK 293T cells. Biochemical studies revealed that the tandem UBA domains of USP5 and the C-terminal Ub-fold domain (UFD) of UbE1 directly interacted with the C-terminal UbL domain of DC-UbP but on the distinct surfaces. Overexpression of DC-UbP in HEK 293T cells enhanced the association of these two enzymes and thus prompted cellular ubiquitination, whereas knockdown of the protein reduced the cellular ubiquitination level. Together, DC-UbP may integrate the functions of USP5 and UbE1 through interacting with them, and thus reconcile the cellular ubiquitination and deubiquitination processes.
- Published
- 2014
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