DNAJB4 Human
Description
Functional Roles in Cellular Homeostasis
DNAJB4 acts as a co-chaperone for HSP70 (e.g., HSPA1A/B), stimulating ATP hydrolysis and facilitating protein folding or degradation. Key roles include:
Protein Quality Control
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Client Protein Assistance: Binds misfolded proteins and directs them to HSP70 for refolding or degradation.
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ER-Associated Degradation: Targets misfolded E-cadherin to the endoplasmic reticulum for degradation .
Stress Response
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Heat Shock Regulation: Expression increases under proteotoxic stress (e.g., heat shock, HSP90 inhibitors) .
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m6A RNA Modifications: HSP90 inhibitors (e.g., ganetespib) upregulate DNAJB4 translation via N 6-methyladenosine (m6A) modifications at adenosine 114 in its 5′-UTR .
Cancer Implications
DNAJB4 is recognized as a tumor suppressor, with downregulated expression linked to poor prognosis in multiple cancers.
Muscular Diseases
DNAJB4 mutations are implicated in novel chaperonopathies, particularly affecting striated muscle.
Regulatory Mechanisms
DNAJB4 expression is dynamically regulated through post-transcriptional and epigenetic pathways:
Epitranscriptomic Regulation
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m6A Modifications:
HSP90 Inhibitor Response
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Ganetespib Treatment: Induces a ~30-fold increase in DNAJB4 protein levels, surpassing mRNA upregulation, highlighting post-transcriptional control .
Research Applications
DNAJB4 is utilized in preclinical models to study disease mechanisms and therapeutic strategies:
Product Specs
Q&A
DNAJB4 (DnaJ Heat Shock Protein Family Member B4) is a molecular chaperone implicated in cancer progression and therapeutic response. Below are structured FAQs addressing key research considerations, integrating findings from clinical studies, molecular mechanisms, and experimental approaches.
Advanced Research Questions
How to resolve contradictions in DNAJB4’s role across cancer types?
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Analysis framework:
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Compare TCGA pan-cancer data (TIMER2.0) for DNAJB4 expression vs. survival (p < 0.05) .
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Example:
Cancer Type DNAJB4 Expression Prognostic Impact Breast Low Poor OS (HR = 1.8) Lung High Favorable PFS (HR = 0.6) Melanoma Low Increased metastasis -
Mechanistic studies: Use tissue-specific CRISPR models to dissect context-dependent interactions (e.g., Src SH3 domains in lung cancer) .
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How do HSP90 inhibitors regulate DNAJB4 via epitranscriptomic mechanisms?
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Method:
How to evaluate DNAJB4’s immunomodulatory effects in vivo?
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Protocol:
Data Contradiction & Validation
Why do miR-183-5p and DNAJB4 show inverse correlations in some datasets?
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Resolution strategy:
Therapeutic Development
Can DNAJB4 be leveraged to overcome HSP90 inhibitor resistance?
Product Science Overview
DNAJB4 is a molecular chaperone that assists in the proper folding of proteins and the degradation of misfolded proteins. It is known to bind to the cell adhesion protein E-cadherin, targeting it to the plasma membrane. Additionally, DNAJB4 binds incorrectly folded E-cadherin and directs it for endoplasmic reticulum-associated degradation .
The protein is involved in several cellular processes, including:
- Protein folding: DNAJB4 stimulates ATP hydrolysis and the folding of unfolded proteins mediated by HSPA1A/B .
- Tumor suppression: DNAJB4 acts as a tumor suppressor, particularly in colorectal carcinoma. Downregulation of this gene may serve as a biomarker for predicting patient outcomes .
- Cellular stress response: As a member of the heat shock protein family, DNAJB4 helps cells cope with stress by preventing the aggregation of misfolded proteins .
Mutations or alterations in the DNAJB4 gene have been associated with various diseases, including:
