ArticleThe Journal of biological chemistry2022
Heat shock protein Hspa13 regulates endoplasmic reticulum and cytosolic proteostasis through modulation of protein translocation.
Article in The Journal of biological chemistry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 14 citations in OpenAlex.
- Macrophage RSAD2 Couples mtDNA Synthesis With a Self-Amplifying Inflammatory Circuit to Orchestrate Tissue Repair.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Systematic comparison of temporal hepatotoxicant-induced gene network responses across 3 liver test systems.Toxicological sciences : an official journal of the Society of Toxicology · 2026Article
- Recent insights into HSP70: proteostasis and beyond.Frontiers in molecular biosciences · 2026Review
- Characterization and Evolutionary Analysis of Non-Canonical Heat Shock Protein 70 Family Members in Metazoan.International journal of molecular sciences · 2025Article
- Hspa13 Deficiency Impaired Marginal Zone B Cells Regulatory Function and Contributed to Lupus Pathogenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Dysregulation of N-glycosylation byInternational journal of biological sciences · 2025Article
- Integrative bulk and single-cell transcriptome analyses reveal integrated stress response-related biomarkers in periodontitis with experimental validation.Frontiers in immunology · 2025Article
- Article
- Knockdown of HSPA13 Inhibits TGFβ1-Induced Epithelial-Mesenchymal Transition of RPE by Suppressing the PI3K/Akt Signaling Pathway.Investigative ophthalmology & visual science · 2024Article
- Comparative analysis of SEC61A1 mutant R236C in two patient-derived cellular platforms.Scientific reports · 2024Article
- Is It Still Possible to Think about HSP70 as a Therapeutic Target in Onco-Hematological Diseases?Biomolecules · 2023Review
- Quantitative Measurement of Transthyretin Mistargeting by Proximity Labeling and Parallel Reaction Monitoring.Frontiers in chemical biology · 2023Article
- Closest horizons of Hsp70 engagement to manage neurodegeneration.Frontiers in molecular neuroscience · 2023Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Most eukaryotic secretory proteins are cotranslationally translocated through Sec61 into the endoplasmic reticulum (ER). Because these proteins have evolved to fold in the ER, their mistargeting is associated with toxicity. Genetic experiments have implicated the ER heat shock protein 70 (Hsp70) Hspa13/STCH as involved in processing of nascent secretory proteins. Herein, we evaluate the role of Hspa13 in protein import and the maintenance of cellular proteostasis in human cells, primarily using the human embryonic kidney 293T cell line. We find that Hspa13 interacts primarily with the Sec61 translocon and its associated factors. Hspa13 overexpression inhibits translocation of the secreted protein transthyretin, leading to accumulation and aggregation of immature transthyretin in the cytosol. ATPase-inactive mutants of Hspa13 further inhibit translocation and maturation of secretory proteins. While Hspa13 overexpression inhibits cell growth and ER quality control, we demonstrate that HSPA13 knockout destabilizes proteostasis and increases sensitivity to ER disruption. Thus, we propose that Hspa13 regulates import through the translocon to maintain both ER and cytosolic protein homeostasis. The raw mass spectrometry data associated with this article have been deposited in the PRIDE archive and can be accessed at PXD033498.
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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 Socratic graph.