ArticleMolecular & cellular proteomics : MCP2018
Proteomics Reveals Scope of Mycolactone-mediated Sec61 Blockade and Distinctive Stress Signature.
Article in Molecular & cellular proteomics : MCP, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 73 citations in OpenAlex.
- Aberrant stromal tissue factor localisation and mycolactone-driven vascular dysfunction, exacerbated by IL-1β, are linked to fibrin formation in Buruli ulcer lesions.PLoS pathogens · 2022Trial
- Pairwise transmembrane domain insertion during multipass protein biogenesis.Molecular cell · 2026Article
- Membrane Protein Insertion in Cells: Principles, Pathways, and Quality Control.Chemical reviews · 2026Review
- Identification of Hoiamide A as an Inducer of Oxidative and Endoplasmic Reticulum Secretory Pathway Stress.Journal of natural products · 2026Article
- Global analysis of translocon remodeling during protein synthesis at the ER.Nature structural & molecular biology · 2025Article
- Successful treatment with joint retention of Mycobacterium ulcerans prosthetic joint infection in a patient with rheumatoid arthritis.PLoS neglected tropical diseases · 2025Article
- Article
- TheeLife · 2025Article
- Toward Understanding the Mechanism of Client-Selective Small Molecule Inhibitors of the Sec61 Translocon.Journal of molecular recognition : JMR · 2025Review
- The prolyl isomerase FKBP11 is a secretory translocon accessory factor.Molecular biology of the cell · 2024Article
- Mycolactone causes destructive Sec61-dependent loss of the endothelial glycocalyx and vessel basement membrane: a new indirect mechanism driving tissue necrosis inbioRxiv : the preprint server for biology · 2024Article
- Article
- Diastereomers of Coibamide A Show Altered Sec61 Client Selectivity and Ligand-Dependent Activity against Patient-Derived Glioma Stem-like Cells.ACS pharmacology & translational science · 2024Article
- Review
- The Biogenesis of Multipass Membrane Proteins.Cold Spring Harbor perspectives in biology · 2023Review
- Sec61 blockade therapy overrides resistance to proteasome inhibitors and immunomodulatory drugs in multiple myeloma.Frontiers in oncology · 2023Article
- Quantitative Measurement of Transthyretin Mistargeting by Proximity Labeling and Parallel Reaction Monitoring.Frontiers in chemical biology · 2023Article
- Article
- Genome-wide screening identified SEC61A1 as an essential factor for mycolactone-dependent apoptosis in human premonocytic THP-1 cells.PLoS neglected tropical diseases · 2022Article
- Article
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Authors and funding
10 authors at 5 institutions in 4 countries.
Funding
Abstract
Mycolactone is a bacteria-derived macrolide that blocks the biogenesis of a large array of secretory and integral transmembrane proteins (TMP) through potent inhibition of the Sec61 translocon. Here, we used quantitative proteomics to delineate the direct and indirect effects of mycolactone-mediated Sec61 blockade in living cells. In T lymphocytes, dendritic cells and sensory neurons, Sec61 substrates downregulated by mycolactone were in order of incidence: secretory proteins (with a signal peptide but no transmembrane domain), TMPs with a signal peptide (Type I) and TMPs without signal peptide and a cytosolic N terminus (Type II). TMPs without a signal peptide and the opposite N terminus topology (Type III) were refractory to mycolactone inhibition. This rule applied comparably to single- and multi-pass TMPs, and extended to exogenous viral proteins. Parallel to its broad-spectrum inhibition of Sec61-mediated protein translocation, mycolactone rapidly induced cytosolic chaperones Hsp70/Hsp90. Moreover, it activated an atypical endoplasmic reticulum stress response, differing from conventional unfolded protein response by the down-regulation of Bip. In addition to refining our mechanistic understanding of Sec61 inhibition by mycolactone, our findings thus reveal that Sec61 blockade induces proteostatic stress in the cytosol and the endoplasmic reticulum.
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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.