title: FAT10ylation as a signal for proteasomal degradation.
abstract: The Nobel prize has been awarded for the discovery of ubiquitin as a transferable signal for the degradation of proteins by the 26S proteasome. While isopeptide linkage of a protein with a single ubiquitin does not serve as a degradation signal for the proteasome, poly-ubiquitylation via several different lysine residues within ubiquitin leads to efficient proteasomal degradation. Ubiquitin-like modifiers have not been shown to directly mediate proteasomal degradation except for the cytokine inducible modifier HLA-F adjacent transcript 10 (FAT10), which consists of two ubiquitin-like domains. FAT10 ends with a free diglycine motif at its C-terminus which is required for isopeptide linkage to hundreds of different substrates. In contrast to ubiquitin, a single FAT10 suffices to bind to the 26S proteasome and to efficiently mediate proteasomal degradation in a ubiquitin-independent manner. Here we review the data on ubiquitin-independent degradation by FAT10, on how FAT10 is conjugated to its substrates, how FAT10 binds to the 26S proteasome, and how the ubiquitin-like (UBL)-ubiquitin-associated (UBA) protein NUB1L accelerates FAT10 mediated proteolysis. Finally, with a glimpse on recently identified substrates, we will discuss the currently emerging knowledge about the biological functions of FAT10. This article is part of a Special Issue entitled: Ubiquitin-Proteasome System. Guest Editors: Thomas Sommer and Dieter H. Wolf.
authors: Division of Immunology, Department of Biology, University of Konstanz, D-78457 Konstanz, Germany.
authors: Gunter
authors: G
authors: Schmidtke
authors: Annette
authors: A
authors: Aichem
authors: Marcus
authors: M
authors: Groettrup
mesh_terms: D000818:Animals; D006801:Humans; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D021382:Protein Sorting Signals / Q000502:physiology; D059748:Proteolysis; D054875:Ubiquitination / Q000502:physiology*; D014452:Ubiquitins / Q000378:metabolism*
chemical_list: D021382:Protein Sorting Signals; C109184:UBD protein, human; D014452:Ubiquitins; D046988:Proteasome Endopeptidase Complex
keywords: Degradation; FAT10; NUB1L; Proteasome; Ubiquitin