Direct proteasome binding and subsequent degradation of unspliced XBP-1 prevent its intracellular aggregation

8Citations
Citations of this article
23Readers
Mendeley users who have this article in their library.

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. Structured summary: MINT-7302217: XBP1-u (uniprotkb:P17861-1) binds (MI:0407) to Proteasome subunit alpha 7.2 (uniprotkb:O14818) by pull down (MI:0096). MINT-7302148: Vimentin (uniprotkb:P08670) and XBP1-u (uniprotkb:P17861-1) colocalize (MI:0403) by fluorescence microscopy (MI:0416). MINT-7302163: XBP1-u (uniprotkb:P17861-1) binds (MI:0407) to Proteasome subunit alpha 5 (uniprotkb:P28066) by pull down (MI:0096). MINT-7302186: XBP1-u (uniprotkb:P17861-1) binds (MI:0407) to Proteasome subunit alpha 6 (uniprotkb:P60900) by pull down (MI:0096). © 2009 Federation of European Biochemical Societies.

Cite

CITATION STYLE

APA

Navon, A., Gatushkin, A., Zelcbuch, L., Shteingart, S., Farago, M., Hadar, R., & Tirosh, B. (2010). Direct proteasome binding and subsequent degradation of unspliced XBP-1 prevent its intracellular aggregation. FEBS Letters, 584(1), 67–73. https://doi.org/10.1016/j.febslet.2009.11.069

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free