ArticleThe Journal of biological chemistry2009
The Endoplasmic Reticulum-associated Degradation of Transthyretin Variants Is Negatively Regulated by BiP in Mammalian Cells.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 33 citations in OpenAlex.
- Molecular mechanisms and emerging therapies in wild-type transthyretin amyloid cardiomyopathy.Heart failure reviews · 2024Review
- Heat shock protein Hspa13 regulates endoplasmic reticulum and cytosolic proteostasis through modulation of protein translocation.The Journal of biological chemistry · 2022Article
- The Journey of Human Transthyretin: Synthesis, Structure Stability, and Catabolism.Biomedicines · 2022Review
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- Article
- Chaperoning Endoplasmic Reticulum-Associated Degradation (ERAD) and Protein Conformational Diseases.Cold Spring Harbor perspectives in biology · 2019Review
- Article
- Viperin Targets Flavivirus Virulence by Inducing Assembly of Noninfectious Capsid Particles.Journal of virology · 2018Article
- Article
- Familial prion protein mutants inhibit Hrd1-mediated retrotranslocation of misfolded proteins by depleting misfolded protein sensor BiP.Human molecular genetics · 2016Article
- Propofol Decreases Endoplasmic Reticulum Stress-Mediated Apoptosis in Retinal Pigment Epithelial Cells.PloS one · 2016Article
- Lysozyme Mutants Accumulate in Cells while Associated at their N-terminal Alpha-domain with the Endoplasmic Reticulum Chaperone GRP78/BiP.International journal of biological sciences · 2016Article
- Different Roles of GRP78 on Cell Proliferation and Apoptosis in Cartilage Development.International journal of molecular sciences · 2015Article
- ATF6 activation reduces the secretion and extracellular aggregation of destabilized variants of an amyloidogenic protein.Chemistry & biology · 2014Article
- Stress-independent activation of XBP1s and/or ATF6 reveals three functionally diverse ER proteostasis environments.Cell reports · 2013Article
- Transthyretin binds to glucose-regulated proteins and is subjected to endocytosis by the pancreatic β-cell.Cellular and molecular life sciences : CMLS · 2012Article
- Intracellular trafficking and secretion of mouse mesencephalic astrocyte-derived neurotrophic factor.Molecular and cellular biochemistry · 2012Article
- Protein C mutation (A267T) results in ER retention and unfolded protein response activation.PloS one · 2011Article
- ANKRD13C acts as a molecular chaperone for G protein-coupled receptors.The Journal of biological chemistry · 2010Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Amyloid fibril formation of mutant transthyretin (TTR) that causes familial amyloid polyneuropathy occurs in the extracellular space. Thus, secretion of TTR variants contributes to the pathogenesis of amyloidosis. However, the molecular mechanisms underlying the endoplasmic reticulum (ER) exit or retention and subsequent degradation of TTR variants remain unclear. Here, we demonstrated that the nonsecreted TTR variants, such as D18G TTR and amyloidogenic TTRs with introduced monomeric mutation (M-TTRs), stably interact with the ER chaperone BiP in mammalian cells. These proteins were co-secreted with the secreted form of BiP in which the KDEL signal was removed, indicating that BiP partially contributes to the ER retention of nonsecreted TTR variants. More interestingly, the degradation efficiency of nonsecreted TTRs was increased when BiP was down-regulated by small interfering RNA. Thus, BiP protects the TTR variants from immediate degradation. Additionally, we showed that the stability of nonsecreted TTR variants is not disturbed in the coat complex II-deficient conditions, which are enough to inhibit the ER export of secreted TTR variants, including wild-type TTR. Therefore, the post-ER retrieval mechanism might not contribute to the ER-associated degradation of nonsecreted TTR variants. These findings suggest that the affinity to the ER-resident protein BiP regulates the fate of TTR variants in the ER.
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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.