ArticleThe Journal of biological chemistry2013
Endoplasmic reticulum protein quality control is determined by cooperative interactions between Hsp/c70 protein and the CHIP E3 ligase.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
45 citing papers in PubMed, 67 citations in OpenAlex.
- HSP90 shields ROC1/RBX1 from proteasomal degradation by CHIP E3 ubiquitin ligase to promote lung adenocarcinoma.Signal transduction and targeted therapy · 2026Article
- NSP1 of Alongshan virus antagonizes type I interferon responses by promoting STUB1-mediated degradation of RIG-I.Cell communication and signaling : CCS · 2026Article
- ARCN1 suppresses innate immune responses against respiratory syncytial virus by promoting STUB1-mediated IKKε degradation.PLoS pathogens · 2025Article
- Metabolic functions for molecular chaperones and stress proteins in microcephaly.Cellular and molecular life sciences : CMLS · 2025Review
- A nanobody that binds to the backside of the ubiquitin conjugating enzyme Ube2G2 differentially affects interactions with its partner E3 Ligases.Communications biology · 2025Article
- New insights into the role of ubiquitination in angiogenesis (Review).International journal of molecular medicine · 2025Review
- RNA-seq revealed the effects of heat stress on different brain regions ofFrontiers in physiology · 2025Article
- Rescue of mitochondrial import failure by intercellular organellar transfer.Nature communications · 2024Article
- Article
- Control of SOX2 protein stability and tumorigenic activity by E3 ligase CHIP in esophageal cancer cells.Oncogene · 2023Article
- Association betweenGenes · 2023Article
- Mortalin: Protein partners, biological impacts, pathological roles, and therapeutic opportunities.Frontiers in cell and developmental biology · 2023Review
- Effect of evolution of the C-terminal region on chaperone activity of Hsp70.Protein science : a publication of the Protein Society · 2023Article
- Protein network analysis to prioritize key genes in amyotrophic lateral sclerosis.IBRO neuroscience reports · 2022Article
- Hsp70 in Redox Homeostasis.Cells · 2022Review
- Proximity Profiling of the CFTR Interaction Landscape in Response to Orkambi.International journal of molecular sciences · 2022Article
- CHIP/STUB1 Ubiquitin Ligase Functions as a Negative Regulator of ErbB2 by Promoting Its Early Post-Biosynthesis Degradation.Cancers · 2021Article
- Inward Outward Signaling in Ovarian Cancer: Morpho-Phospho-Proteomic Profiling Upon Application of Hypoxia and Shear Stress Characterizes the Adaptive Plasticity of OVCAR-3 and SKOV-3 Cells.Frontiers in oncology · 2021Article
- Spinocerebellar ataxia type 48: last but not least.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2020Review
- Ubiquitination in the ERAD Process.International journal of molecular sciences · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
The C terminus of Hsp70 interacting protein (CHIP) E3 ligase functions as a key regulator of protein quality control by binding the C-terminal (M/I)EEVD peptide motif of Hsp/c70(90) with its N-terminal tetratricopeptide repeat (TPR) domain and facilitating polyubiquitination of misfolded client proteins via its C-terminal catalytic U-box. Using CFTR as a model client, we recently showed that the duration of the Hsc70-client binding cycle is a primary determinant of stability. However, molecular features that control CHIP recruitment to Hsp/c70, and hence the fate of the Hsp/c70 client, remain unknown. To understand how CHIP recognizes Hsp/c70, we utilized a dominant negative mutant in which loss of a conserved proline in the U-box domain (P269A) eliminates E3 ligase activity. In a cell-free reconstituted ER-associated degradation system, P269A CHIP inhibited Hsc70-dependent CFTR ubiquitination and degradation in a dose-dependent manner. Optimal inhibition required both the TPR and the U-box, indicating cooperativity between the two domains. Neither the wild type nor the P269A mutant changed the extent of Hsc70 association with CFTR nor the dissociation rate of the Hsc70-CFTR complex. However, the U-box mutation stimulated CHIP binding to Hsc70 while promoting CHIP oligomerization. CHIP binding to Hsc70 binding was also stimulated by the presence of an Hsc70 client with a preference for the ADP-bound state. Thus, the Hsp/c70 (M/I)EEVD motif is not a simple anchor for the TPR domain. Rather CHIP recruitment involves reciprocal allosteric interactions between its TPR and U-box domains and the substrate-binding and C-terminal domains of Hsp/c70.
Indexed as
Identifiers
What OpenQuestion holds
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.