CIRBP Human
Description
Molecular Structure and Isoforms
CIRBP exists in two major splice variants generated through N6-methyladenosine-mediated alternative splicing :
| Isoform | Amino Acids | Key Domains | Functional Features |
|---|---|---|---|
| CIRBP-L | 297 | RRM, RGG, ASR | Enhances telomerase activity, stabilizes HIF-1α mRNA |
| CIRBP-S | 172 | RRM, RGG | Modulates p27 expression, cell cycle control |
RRM: RNA-recognition motif; RGG: Arginine-rich motif; ASR: Alternatively spliced region
Both isoforms contain RNA-binding domains but differ in their capacity to interact with specific mRNA targets. The ASR motif in CIRBP-L enables unique protein-protein interactions critical for telomerase complex formation .
Mechanisms of Action
CIRBP regulates gene expression through:
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mRNA stability modulation: Binds 3'-UTRs of targets like HIF-1α, cyclin E1, and TERT, extending their half-lives under stress
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Translation control: Enhances ribosomal loading on transcripts via ERK and NF-κB pathway activation
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Protein partnerships: Interacts with DYRK1B to stabilize cyclin D1 and inhibit p27 phosphorylation
Key molecular interactions identified via STRING database analysis :
| Partner Protein | Interaction Score | Biological Role |
|---|---|---|
| HNRNPK | 0.880 | Pre-mRNA processing, p53 regulation |
| TLR4 | 0.854 | Innate immune response |
| PRMT1 | 0.768 | Arginine methylation, transcriptional activation |
Dual Roles in Cancer Pathology
Clinical studies reveal context-dependent oncogenic and tumor-suppressive functions:
Pro-Tumorigenic Effects
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Breast cancer: Upregulates cyclin E1 (HR = 2.1, p < 0.01) and correlates with luminal subtype progression
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Pancreatic ductal adenocarcinoma: High expression associates with poor differentiation (p = 0.003) and reduced median survival (10 vs. 38 months, p < 0.001)
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Telomere maintenance: Stabilizes TERT mRNA, increasing telomerase activity by 3.8-fold in vitro
Tumor-Suppressive Activity
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Induces p27-mediated cell cycle arrest in fibroblasts (G0/G1 phase increase: 58% → 72%)
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Downregulates CST3 in breast cancer models, reducing metastatic potential
Clinical Applications and Biomarker Potential
Recent translational studies demonstrate clinical relevance:
A phase I feasibility study (n=19) confirmed CIRBP detectability in 100% of pediatric surgical patients, with postoperative levels rising 2.3-fold from baseline .
Recombinant Protein Development
Commercial CIRBP variants enable functional studies :
| Parameter | Specification |
|---|---|
| Expression Host | HEK293T |
| Purity | >80% (SDS-PAGE verified) |
| Activity | Binds 3'-UTR elements (KD = 12 nM) |
| Storage | -80°C in 25 mM Tris-HCl, 10% glycerol |
This recombinant protein (NP_001271) has been instrumental in mapping stress granule assembly mechanisms and telomerase regulation pathways .
Therapeutic Targeting Challenges
Current research gaps include:
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Isoform-specific functional divergence in human malignancies
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Tissue-dependent effects on inflammatory pathways (e.g., NLRP3 activation vs. TRX-mediated ROS reduction)
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Lack of selective inhibitors for oncogenic CIRBP-L isoform
Ongoing clinical trials (NCT04811260) are evaluating anti-CIRBP antibodies in sepsis management, with preliminary results showing 40% reduction in cytokine storm severity .
Product Specs
RDSYDSYATH NE.
Product Science Overview
CIRBP functions primarily as a translational activator and is essential for the cold-induced suppression of cell proliferation . When cells are exposed to mild hypothermia, CIRBP expression is induced, which helps in stabilizing mRNA transcripts and promoting cell survival. This induction is mediated by a specific regulatory sequence in the 5′ flanking region of the CIRBP gene, known as the mild-cold responsive element (MCRE). The transcription factor Sp1 binds to this element, enhancing CIRBP expression at lower temperatures .
Recombinant CIRBP is produced using recombinant DNA technology, which allows for the expression and purification of this protein in various host organisms. This technology has made it feasible to produce CIRBP in large quantities, which is particularly useful for research and potential therapeutic applications. The expression of recombinant proteins, including CIRBP, can be optimized using cold-shock promoters, which are genetic elements that respond to low temperatures and enhance protein expression .
The ability to produce recombinant CIRBP has several important applications:
- Research: Recombinant CIRBP is used in research to study its role in cellular stress responses, particularly in understanding how cells adapt to cold environments.
- Therapeutics: There is potential for using CIRBP in therapeutic applications, especially in conditions where enhancing cell survival under stress is beneficial.
- Biotechnology: Cold-shock promoters and CIRBP can be utilized to improve the yield of other recombinant proteins in mammalian cells, making them valuable tools in biotechnology .
