ArticleThe EMBO journal2014
Signal peptide peptidase functions in ERAD to cleave the unfolded protein response regulator XBP1u.
Article in The EMBO journal, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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Who cites it
71 citing papers in PubMed, 112 citations in OpenAlex.
- Ubiquitin and ubiquitin-like modifications in the endoplasmic reticulum stress response.The FEBS journal · 2026Review
- Comparative analysis of Cdc48-dependent proteolysis at the ER, mitochondria and chloroplasts.Nature communications · 2026Review
- Dimeric architecture and membrane thinning govern substrate recognition by human signal peptide peptidase.Research square · 2026Article
- Functional Characterization of a Signal Peptide Peptidase inInternational journal of molecular sciences · 2026Article
- Conformational Flexibility of Transmembrane Helices: How it Works and Where it Matters.Chemical reviews · 2026Review
- Signal peptide peptidase- and SPP-like 3-dependent shedding of α1,6-fucosyltransferase differentially affects core fucosylation.The Journal of biological chemistry · 2026Article
- The role of ER-associated degradation and ER-phagy in health and disease.Signal transduction and targeted therapy · 2026Review
- Structural insights into human signal peptide peptidase.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- SPLiCR-seq: A CRISPR-Based Screening Platform for RNA splicing Identifies Novel Regulators of IRE1α-XBP1 Signaling Under ER Stress.Nature communications · 2025Article
- Macrophage HM13/SPP Enhances Foamy Macrophage Formation and Atherogenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The N-terminal PA domains of signal-peptide-peptidase-like 2 (SPPL2) proteases impact on TNFα cleavage.Communications biology · 2025Article
- Druggable genome screens identify SPP as an antiviral host target for multiple flaviviruses.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Topology surveillance of the lanosterol demethylase CYP51A1 by signal peptide peptidase.Journal of cell science · 2024Article
- Selective regulation of aspartyl intramembrane protease activity by calnexin.Cellular and molecular life sciences : CMLS · 2024Article
- SANS reveals lipid-dependent oligomerization of an intramembrane aspartyl protease from H. volcanii.Biophysical journal · 2024Article
- Genome-Wide Identification of the SPP/SPPL Gene Family andInternational journal of molecular sciences · 2024Article
- Signal Peptide Peptidase and PI4Kβ1/2 play opposite roles in plant ER stress response and immunity.Stress biology · 2024Article
- The endoplasmic reticulum: Homeostasis and crosstalk in retinal health and disease.Progress in retinal and eye research · 2024Review
- Nascent Chain Ubiquitination is Uncoupled from Degradation to Enable Protein Maturation.bioRxiv : the preprint server for biology · 2023Article
- Mechanisms of substrate processing during ER-associated protein degradation.Nature reviews. Molecular cell biology · 2023Review
11 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Signal peptide peptidase (SPP) catalyzes intramembrane proteolysis of signal peptides at the endoplasmic reticulum (ER), but has also been suggested to play a role in ER-associated degradation (ERAD). Here, we show that SPP forms a complex with the ERAD factor Derlin1 and the E3 ubiquitin ligase TRC8 to cleave the unfolded protein response (UPR) regulator XBP1u. Cleavage occurs within a so far unrecognized type II transmembrane domain, which renders XBP1u as an SPP substrate through specific sequence features. Additionally, Derlin1 acts in the complex as a substrate receptor by recognizing the luminal tail of XBP1u. Remarkably, this interaction of Derlin1 with XBP1u obviates the need for ectodomain shedding prior to SPP cleavage, commonly required for intramembrane cuts. Furthermore, we show that XBP1u inhibits the UPR transcription factor XBP1s by targeting it toward proteasomal degradation. Thus, we identify an ERAD complex that controls the abundance of XBP1u and thereby tunes signaling through the UPR.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.