ArticleThe EMBO journal2014
Shedding of glycan-modifying enzymes by signal peptide peptidase-like 3 (SPPL3) regulates cellular N-glycosylation.
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 53 papers, 1 of them a synthesis that pooled it.
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53 citing papers in PubMed, 1 synthesis or guideline pooled it, 109 citations in OpenAlex.
- Common variants on 6q16.2, 12q24.31 and 16p13.3 are associated with major depressive disorder.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2018Pooled it
- Glycoengineered Recombinant Alpha1-Antitrypsin Results in Comparable In Vitro and In Vivo Activities to Human Plasma-Derived Protein.Biotechnology and bioengineering · 2026Article
- From Glycocode to Precision Oncology: Therapeutic Strategies Targeting Aberrant O-GalNAc Glycosylation in Cancer.Chemical reviews · 2026Review
- Cancer-associated alterations in O-GalNAc glycosylation.Glycobiology · 2026Review
- Genomic landscape of rare variants in a Chinese autism cohort and discovery of novel risk genes.Molecular psychiatry · 2026Article
- 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 Glycan Structures in Modulating GM-CSF Bioactivity: Insights from Glycoengineering.bioRxiv : the preprint server for biology · 2026Article
- Structural insights into human signal peptide peptidase.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Genome-wide identification of modulators of Chlamydia trachomatis parasitophorous vacuole stability highlights an important role for sphingolipid supply.PLoS biology · 2025Article
- Conformational dynamics and membrane insertion mechanism of B4GALNT1 in ganglioside synthesis.Nature communications · 2025Article
- The N-terminal PA domains of signal-peptide-peptidase-like 2 (SPPL2) proteases impact on TNFα cleavage.Communications biology · 2025Article
- Tumor-Expressed SPPL3 Supports Innate Antitumor Immune Responses.European journal of immunology · 2025Article
- GOLPH3 and GOLPH3L maintain Golgi localization of LYSET and a functional mannose 6-phosphate transport pathway.The EMBO journal · 2024Article
- New players and targets in mannose 6-phosphate-dependent lysosomal sorting.The EMBO journal · 2024Article
- Selective regulation of aspartyl intramembrane protease activity by calnexin.Cellular and molecular life sciences : CMLS · 2024Article
- Regulation of intracellular activity of N-glycan branching enzymes in mammals.The Journal of biological chemistry · 2024Review
- Functional genomics identifies N-acetyllactosamine extension of complex N-glycans as a mechanism to evade lysis by natural killer cells.Cell reports · 2024Article
- Genome-Wide Identification of the SPP/SPPL Gene Family andInternational journal of molecular sciences · 2024Article
- Evaluating the causal relationship between human blood metabolites and gastroesophageal reflux disease.World journal of gastrointestinal oncology · 2023Article
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16 authors at 5 institutions in 1 country.
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Abstract
Protein N-glycosylation is involved in a variety of physiological and pathophysiological processes such as autoimmunity, tumour progression and metastasis. Signal peptide peptidase-like 3 (SPPL3) is an intramembrane-cleaving aspartyl protease of the GxGD type. Its physiological function, however, has remained enigmatic, since presently no physiological substrates have been identified. We demonstrate that SPPL3 alters the pattern of cellular N-glycosylation by triggering the proteolytic release of active site-containing ectodomains of glycosidases and glycosyltransferases such as N-acetylglucosaminyltransferase V, β-1,3 N-acetylglucosaminyltransferase 1 and β-1,4 galactosyltransferase 1. Cleavage of these enzymes leads to a reduction in their cellular activity. In line with that, reduced expression of SPPL3 results in a hyperglycosylation phenotype, whereas elevated SPPL3 expression causes hypoglycosylation. Thus, SPPL3 plays a central role in an evolutionary highly conserved post-translational process in eukaryotes.
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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.