title: Direct proteasome binding and subsequent degradation of unspliced XBP-1 prevent its intracellular aggregation.
abstract: The non-canonical splicing of XBP-1 mRNA is a hallmark of the mammalian unfolded protein response (UPR). The proteasomal degradation of unspliced XBP-1 (XBP-1u) facilitates the termination of the UPR. Thus, understanding the mechanism of XBP-1u degradation may allow control over UPR duration and intensity. We show that XBP-1u interacts with purified 20S proteasomes through its unstructured C-terminus, which leads to its degradation in a manner that autonomously opens the proteasome gate. In living cells, the C-terminus of XBP-1u accumulates in aggresome structures in the presence of proteasome inhibitors. We propose that direct proteasomal degradation of XBP-1u prevents its intracellular aggregation.
authors: Department of Biological Regulation, The Weizmann Institute of Science, Rehovot, Israel.
authors: Ami
authors: A
authors: Navon
authors: Ariel
authors: A
authors: Gatushkin
authors: Lior
authors: L
authors: Zelcbuch
authors: Shimon
authors: S
authors: Shteingart
authors: Marganit
authors: M
authors: Farago
authors: Rivka
authors: R
authors: Hadar
authors: Boaz
authors: B
authors: Tirosh
mesh_terms: D000595:Amino Acid Sequence; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D061988:Proteasome Inhibitors; D012326:RNA Splicing; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination; D000071717:X-Box Binding Protein 1
chemical_list: D004268:DNA-Binding Proteins; D061988:Proteasome Inhibitors; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605543:XBP1 protein, human; D046988:Proteasome Endopeptidase Complex