ArticleThe Journal of cell biology2014
Cleavage by signal peptide peptidase is required for the degradation of selected tail-anchored proteins.
Article in The Journal of cell biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 88 citations in OpenAlex.
- Dimeric architecture and membrane thinning govern substrate recognition by human signal peptide peptidase.Research square · 2026Article
- Hepatitis C virus p7 regulates Core protein processing via signal peptide peptidase to promote virion assembly.Journal of virology · 2026Article
- The role of ER-associated degradation and ER-phagy in health and disease.Signal transduction and targeted therapy · 2026Review
- Organ-Specific Small Protein Networks in 100 kDa Ultrafiltrates: Functional Analysis and Implications for Neuroregenerative Medicine.International journal of molecular sciences · 2025Article
- Macrophage HM13/SPP Enhances Foamy Macrophage Formation and Atherogenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The DNase TREX1 is a substrate of the intramembrane protease SPP with implications for disease pathogenesis.Cellular and molecular life sciences : CMLS · 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
- Haploinsufficiency and Alzheimer's Disease: The Possible Pathogenic and Protective Genetic Factors.International journal of molecular sciences · 2024Review
- Selective regulation of aspartyl intramembrane protease activity by calnexin.Cellular and molecular life sciences : CMLS · 2024Article
- Signal Peptide Peptidase and PI4Kβ1/2 play opposite roles in plant ER stress response and immunity.Stress biology · 2024Article
- Mechanisms of substrate processing during ER-associated protein degradation.Nature reviews. Molecular cell biology · 2023Review
- A signal peptide peptidase is required for ER-symbiosome proximal association and protein secretion.Nature communications · 2023Article
- Heme oxygenase 1 in erythropoiesis: an important regulator beyond catalyzing heme catabolism.Annals of hematology · 2023Review
- The transmembrane domain of Frey1 harbors a transplantable inhibitory motif for intramembrane proteases.Cellular and molecular life sciences : CMLS · 2023Article
- The Endoplasmic Reticulum and the Fidelity of Nascent Protein Localization.Cold Spring Harbor perspectives in biology · 2023Review
- Spf1 and Ste24: quality controllers of transmembrane protein topology in the eukaryotic cell.Frontiers in cell and developmental biology · 2023Review
- Endoplasmic Reticulum-Associated Protein Degradation.Cold Spring Harbor perspectives in biology · 2022Review
- ATP13A1 prevents ERAD of folding-competent mislocalized and misoriented proteins.Molecular cell · 2022Article
- Identification of Heme Oxygenase-1 as a Putative DNA-Binding Protein.Antioxidants (Basel, Switzerland) · 2022Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
The regulated turnover of endoplasmic reticulum (ER)-resident membrane proteins requires their extraction from the membrane lipid bilayer and subsequent proteasome-mediated degradation. Cleavage within the transmembrane domain provides an attractive mechanism to facilitate protein dislocation but has never been shown for endogenous substrates. To determine whether intramembrane proteolysis, specifically cleavage by the intramembrane-cleaving aspartyl protease signal peptide peptidase (SPP), is involved in this pathway, we generated an SPP-specific somatic cell knockout. In a stable isotope labeling by amino acids in cell culture-based proteomics screen, we identified HO-1 (heme oxygenase-1), the rate-limiting enzyme in the degradation of heme to biliverdin, as a novel SPP substrate. Intramembrane cleavage by catalytically active SPP provided the primary proteolytic step required for the extraction and subsequent proteasome-dependent degradation of HO-1, an ER-resident tail-anchored protein. SPP-mediated proteolysis was not limited to HO-1 but was required for the dislocation and degradation of additional tail-anchored ER-resident proteins. Our study identifies tail-anchored proteins as novel SPP substrates and a specific requirement for SPP-mediated intramembrane cleavage in protein turnover.
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Registered trials
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.