ArticleProceedings of the National Academy of Sciences of the United States of America2012
SGTA antagonizes BAG6-mediated protein triage.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
61 citing papers in PubMed, 95 citations in OpenAlex.
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- Rules of Engagement for Components of Membrane Protein Biogenesis at the Human Endoplasmic Reticulum.International journal of molecular sciences · 2025Review
- The role of ubiquitination in health and disease.MedComm · 2024Review
- Investigation of Glycosylphosphatidylinositol (GPI)-Plasma Membrane Interaction in Live Cells and the Influence of GPI Glycan Structure on the Interaction.Chemistry (Weinheim an der Bergstrasse, Germany) · 2024Article
- Proteotoxic stresses stimulate dissociation of UBL4A from the tail-anchored protein recognition complex.The Biochemical journal · 2023Article
- Chasing the right tail: How the ER membrane complex recognizes its substrates.The Journal of cell biology · 2023Article
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- A second chance for protein targeting/folding: Ubiquitination and deubiquitination of nascent proteins.BioEssays : news and reviews in molecular, cellular and developmental biology · 2022Review
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- Mitochondrial antiviral-signalling protein is a client of the BAG6 protein quality control complex.Journal of cell science · 2022Article
- Targeting of Proteins for Translocation at the Endoplasmic Reticulum.International journal of molecular sciences · 2022Review
- USP5 enhances SGTA mediated protein quality control.PloS one · 2022Article
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- Looking for a safe haven: tail-anchored proteins and their membrane insertion pathways.Plant physiology · 2021Review
- A conserved guided entry of tail-anchored pathway is involved in the trafficking of a subset of membrane proteins in Plasmodium falciparum.PLoS pathogens · 2021Article
- Capture and delivery of tail-anchored proteins to the endoplasmic reticulum.The Journal of cell biology · 2021Review
- An alternative pathway for membrane protein biogenesis at the endoplasmic reticulum.Communications biology · 2021Article
1 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The BAG6 complex was first identified as an upstream loading factor for tail-anchored membrane proteins entering the TRC40-dependent pathway for posttranslational delivery to the endoplasmic reticulum. Subsequently, BAG6 was shown to enhance the proteasomal degradation of mislocalized proteins by selectively promoting their ubiquitination. We now show that the BAG6-dependent ubiquitination of mislocalized proteins is completely reversible and identify a pivotal role for the small glutamine-rich tetratricopeptide repeat-containing protein α (SGTA) in specifically antagonizing this process. SGTA does not simply mask the exposed hydrophobic transmembrane domain of a mislocalized protein, thereby preventing BAG6 recruitment. Rather, SGTA actively promotes the deubiquitination of mislocalized proteins that are already covalently modified, thus reversing the actions of BAG6 and inhibiting its capacity to promote substrate-specific degradation. This SGTA-mediated effect is independent of its tetratricopeptide motifs, suggesting it does not require the actions of Hsp70 and Hsp90 chaperones. These data reveal that, in a cellular context, mislocalized protein ubiquitination is the result of a dynamic equilibrium reflecting competition between pathways that promote either protein maturation or degradation. The targeted perturbation of this equilibrium, achieved by increasing steady-state SGTA levels, results in a specific stabilization of a model mislocalized protein derived from the amyloid precursor protein, an effect that is completely negated by ensuring efficient precursor delivery to the endoplasmic reticulum. We speculate that a BAG6/SGTA cycle operates during protein maturation and quality control in the cytosol and that together these components dictate the fate of a specific subset of newly synthesized proteins.
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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.