ArticleNature2011
Protein targeting and degradation are coupled for elimination of mislocalized proteins.
Article in Nature, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 176 papers.
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Who cites it
176 citing papers in PubMed, 278 citations in OpenAlex.
- Trial
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- A mitochondria-driven quality control mechanism for peroxisomal membrane proteins.Nature communications · 2026Article
- GET3 regulates apoptosis via tail-anchoring of MCL1.Cell death and differentiation · 2026Article
- Mitochondria serve as a holdout compartment for aggregation-prone proteins hindering efficient degradation.Nature communications · 2026Article
- Tubulin hyperglutamylation induces retinal degeneration by disrupting ciliary architecture and protein trafficking.Zoological research · 2026Article
- A conformation-dependent hydrophobic degron determines Rab9a-mediated vesicular trafficking.The Journal of biological chemistry · 2026Article
- Sec61β maintains cytoplasmic proteostasis via ARIH1-mediated translational repression upon ER stress.EMBO reports · 2026Article
- Assembly of Macromolecular Complexes in the Whole-Cell Model of a Minimal Cell.The journal of physical chemistry. B · 2026Article
- X-linked hyper IgM syndrome with a novel CD40-ligand gene mutation suffered from infection of Talaromyces marneffei.Frontiers in immunology · 2026Article
- The degradation of extended protein isoforms points to a misfiring translation initiation process.Molecular genetics and genomics : MGG · 2025Article
- Degrons: defining the rules of protein degradation.Nature reviews. Molecular cell biology · 2025Review
- Unveiling histotype-specific biomarkers in ovarian carcinoma using proteomics.Molecular therapy. Oncology · 2025Article
- Msp1 and Pex19-Pex3 cooperate to achieve correct localization of Pex15 to peroxisomes.The FEBS journal · 2025Article
- One BAG Does Not Fit All: Differences and Similarities of BAG Family Members in Mediating Central Nervous System Homeostasis.Biological psychiatry · 2025Review
- Mechanisms suppressing noncoding translation.Trends in cell biology · 2025Review
- Systematic Engineering for Efficient Uric Acid-Degrading Activity in Probiotic YeastACS synthetic biology · 2025Article
- Ubiquitin-Proteasome System Dysregulation in Alzheimer's Disease Impacts Protein Abundance.bioRxiv : the preprint server for biology · 2025Article
116 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
A substantial proportion of the genome encodes membrane proteins that are delivered to the endoplasmic reticulum by dedicated targeting pathways. Membrane proteins that fail targeting must be rapidly degraded to avoid aggregation and disruption of cytosolic protein homeostasis. The mechanisms of mislocalized protein (MLP) degradation are unknown. Here we reconstitute MLP degradation in vitro to identify factors involved in this pathway. We find that nascent membrane proteins tethered to ribosomes are not substrates for ubiquitination unless they are released into the cytosol. Their inappropriate release results in capture by the Bag6 complex, a recently identified ribosome-associating chaperone. Bag6-complex-mediated capture depends on the presence of unprocessed or non-inserted hydrophobic domains that distinguish MLPs from potential cytosolic proteins. A subset of these Bag6 complex 'clients' are transferred to TRC40 for insertion into the membrane, whereas the remainder are rapidly ubiquitinated. Depletion of the Bag6 complex selectively impairs the efficient ubiquitination of MLPs. Thus, by its presence on ribosomes that are synthesizing nascent membrane proteins, the Bag6 complex links targeting and ubiquitination pathways. We propose that such coupling allows the fast tracking of MLPs for degradation without futile engagement of the cytosolic folding machinery.
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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.