ArticleMolecular biology of the cell2003
Recognition of a single transmembrane degron by sequential quality control checkpoints.
Article in Molecular biology of the cell, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 31 citations in OpenAlex.
- A network of chaperones prevents and detects failures in membrane protein lipid bilayer integration.Nature communications · 2019Article
- Assembly-induced folding regulates interleukin 12 biogenesis and secretion.The Journal of biological chemistry · 2017Article
- Targeting Viral Proteostasis Limits Influenza Virus, HIV, and Dengue Virus Infection.Immunity · 2016Article
- ERAD of proteins containing aberrant transmembrane domains requires ubiquitylation of cytoplasmic lysine residues.Journal of cell science · 2015Article
- Dimerization-dependent folding underlies assembly control of the clonotypic αβT cell receptor chains.The Journal of biological chemistry · 2015Article
- A novel UGGT1 and p97-dependent checkpoint for native ectodomains with ionizable intramembrane residue.Molecular biology of the cell · 2015Article
- Protein homeostasis at the plasma membrane.Physiology (Bethesda, Md.) · 2014Review
- Quality control of integral membrane proteins by assembly-dependent membrane integration.Molecular cell · 2013Article
- Protein quality control at the plasma membrane.Current opinion in cell biology · 2011Review
- Quality control for unfolded proteins at the plasma membrane.The Journal of cell biology · 2010Article
- Role of intramembrane charged residues in the quality control of unassembled T-cell receptor alpha-chains at the endoplasmic reticulum.Journal of cell science · 2010Article
- Endoplasmic reticulum-associated degradation of a degron-containing polytopic membrane protein.Molecular membrane biology · 2009Article
- Decreased ER-associated degradation of alpha-TCR induced by Grp78 depletion with the SubAB cytotoxin.The international journal of biochemistry & cell biology · 2008Article
- A novel function of VCP (valosin-containing protein; p97) in the control of N-glycosylation of proteins in the endoplasmic reticulum.Archives of biochemistry and biophysics · 2007Article
- A misassembled transmembrane domain of a polytopic protein associates with signal peptide peptidase.The Biochemical journal · 2004Article
- Misfolded proteins are sorted by a sequential checkpoint mechanism of ER quality control.The Journal of cell biology · 2004Article
- Bsd2 binds the ubiquitin ligase Rsp5 and mediates the ubiquitination of transmembrane proteins.The EMBO journal · 2004Article
- Misfolding diverts CFTR from recycling to degradation: quality control at early endosomes.The Journal of cell biology · 2004Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
To understand the relationship between conformational maturation and quality control-mediated proteolysis in the secretory pathway, we engineered the well-characterized degron from the alpha-subunit of the T-cell antigen receptor (TCRalpha) into the alpha-helical transmembrane domain of homotrimeric type I integral membrane protein, influenza hemagglutinin (HA). Although the membrane degron does not appear to interfere with acquisition of native secondary structure, as assessed by the formation of native intrachain disulfide bonds, only approximately 50% of nascent mutant HA chains (HA(++)) become membrane-integrated and acquire complex N-linked glycans indicative of transit to a post-ER compartment. The remaining approximately 50% of nascent HA(++) chains fail to integrate into the lipid bilayer and are subject to proteasome-dependent degradation. Site-specific cleavage by extracellular trypsin and reactivity with conformation-specific monoclonal antibodies indicate that membrane-integrated HA(++) molecules are able to mature to the plasma membrane with a conformation indistinguishable from that of HA(wt). These apparently native HA(++) molecules are, nevertheless, rapidly degraded by a process that is insensitive to proteasome inhibitors but blocked by lysosomotropic amines. These data suggest the existence in the secretory pathway of at least two sequential quality control checkpoints that recognize the same transmembrane degron, thereby ensuring the fidelity of protein deployment to the plasma membrane.
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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.