PhI p 1
Description
Molecular Structure and Isoforms
PhIP1 belongs to the BRWD family of proteins, characterized by bromodomains and WD40 repeats. Its structural features include:
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Bromodomains: Bind acetylated lysine residues, mediating chromatin remodeling.
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WD40 Repeats: Facilitate protein-protein interactions, critical for scaffolding functions.
PhIP exists in alternative splice forms, with PHIP1 representing the longest isoform. This isoform is expressed in tissues such as the pancreas and plays a role in insulin signaling, though its primary function in postnatal growth occurs independently of insulin/IGF-1 pathways .
Biological Functions
PhIP1 is essential for:
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Postnatal Growth Regulation: Deficiency in PHIP1 leads to severe growth deficits in mice, with a 40% reduction in body weight by weaning .
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Metabolic Homeostasis: PHIP1-deficient mice exhibit hypoglycemia and reduced lifespan (4–5 weeks) .
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Cell Proliferation: PHIP1-deficient mouse embryonic fibroblasts (MEFs) show slower growth despite normal AKT phosphorylation and enhanced proliferation in response to IGF-1 .
Key Experimental Data
| Parameter | Wild-Type Mice | PHIP1-Deficient Mice |
|---|---|---|
| Postnatal Growth | Normal | 40% deficit by weaning |
| Hypoglycemia | No | Yes |
| Lifespan | Normal | 4–5 weeks |
| MEF Growth Rate | Normal | Slower proliferation |
| IGF-1 Response | Normal proliferation | Increased proliferation |
Data derived from murine studies .
Mechanistic Insights
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IGF-1/AKT Independence: PHIP1 regulates growth through pathways distinct from IGF-1/AKT, as AKT phosphorylation remains normal in PHIP1-deficient MEFs .
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Hypoglycemia Pathogenesis: The metabolic defect in PHIP1-deficient mice suggests a role in glucose homeostasis, potentially involving pancreatic β-cell function or insulin sensitivity .
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Cancer Implications: While PHIP is overexpressed in metastatic melanomas and glioblastomas , PHIP1-specific roles in oncogenesis remain under investigation.
Clinical and Therapeutic Implications
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Growth Disorders: PHIP1 mutations may contribute to human growth deficiencies, though no clinical associations have been established.
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Cancer Biomarker: PHIP overexpression is linked to melanoma metastasis and survival outcomes , but PHIP1-specific targeting requires further study.
Open Questions and Future Directions
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Tissue-Specific Functions: How PHIP1 regulates growth in specific organs (e.g., liver, pancreas) remains unclear.
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Interactome Mapping: Identification of PHIP1-binding partners could elucidate its scaffolding roles.
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Therapeutic Targeting: Development of isoform-specific inhibitors or activators for PHIP1 in growth disorders or cancer.
Product Specs
The PhI p 1 protein solution is prepared in a buffer consisting of 20mM HEPES (pH 8.0), 200mM NaCl, and 20% glycerol.
2. Validated for use in immunodot assays employing positive and negative serum panels.
Product Science Overview
Pollen allergens are a significant cause of allergic reactions, particularly in individuals with respiratory allergies. One of the major allergens from grass pollen is Phl p 1, which is derived from the pollen of Timothy grass (Phleum pratense). Recombinant Phl p 1 (rPhl p 1) is a non-glycosylated protein produced in Escherichia coli (E. coli) cells that carry a cloned cDNA encoding the Phl p 1 allergen . This recombinant form closely resembles the natural Phl p 1 and is used extensively in allergy diagnostics and research.
The gene encoding Phl p 1 is obtained by reverse transcription on an mRNA template isolated from Timothy grass pollen. This gene is then cloned into a plasmid vector, such as pET23a+, for prokaryotic expression in E. coli . The recombinant protein is purified using techniques like anion exchange and affinity chromatography, resulting in a high-purity product suitable for immunological studies .
Phl p 1 is considered one of the most important species-specific allergens of Timothy grass, followed by Phl p 5 . It binds to Immunoglobulin E (IgE) in the majority of patients with grass pollen allergies, indicating that it shares many of the IgE epitopes with natural group 1 grass pollen allergens . Recombinant Phl p 1 has been shown to bind IgE of more than 90% of grass pollen allergic patients . Its biological activity has been demonstrated through histamine release and skin test experiments .
Recombinant allergens like Phl p 1 are used in immunological test systems for the diagnosis of type I hypersensitivity. These systems involve whole allergen extracts, highly purified allergens from the extracts, and their recombinant analogues obtained by gene engineering techniques . The use of recombinant Phl p 1 in diagnostic assays allows for the precise identification of specific IgE antibodies in patients’ serum, aiding in the accurate diagnosis of grass pollen allergies .
