PHIP Antibodies

Structure of PHIP

PHIP is a large multi-domain scaffold protein with a molecular weight of approximately 320 kDa. This protein has highly conserved structural characteristics in different species, and its molecular weight may vary slightly due to transcript variations or post-translational modifications.

The PHIP protein is composed of 2,862 amino acids, and its tertiary structure forms a flexible scaffold conformation through a series of PH domains, WD40 repeat sequences, and nuclear output signal domains. This protein specifically binds to histone acetylation modification through the bromine domain at the C-terminal, while the PH domain at the N-terminal mediates membrane-lipid interactions and signal transduction. This multi-domain assembly method enables it to synergistically regulate the assembly of transcriptional complexes and membrane receptor signal transduction.

Fig. 1 Scheme of proposed 6-shogaol-inhibited PhIP-induced human renal cell carcinoma bone metastasis.¹

Key structural properties of PHIP:

• Assembly of multiple functional domains
• Hydrophobic regions mediate protein interactions and complex assembly
• Bromine domains specifically recognize histone acetylation modifications

Functions of PHIP

The main function of PHIP protein is to act as a molecular scaffold to participate in transcriptional regulation and signal transduction. In addition, it also involves a variety of cellular processes such as chromatin remodeling, cell cycle regulation and maintenance of metabolic homeostasis.

PHIP forms a dynamic interaction network through its multi-domain assembly, responding to intracellular and extracellular signals in a synergistic manner. Its dysfunction is closely related to cancer, diabetes and neurodevelopmental disorders.

Applications of PHIP and PHIP Antibody in Literature

1. Malik, Durr-e-shahwar, Rhiannon M. David, and Nigel J. Gooderham. "Ethanol potentiates the genotoxicity of the food-derived mammary carcinogen PhIP in human estrogen receptor-positive mammary cells: Mechanistic support for lifestyle factors (cooked red meat and ethanol) associated with mammary cancer." Archives of Toxicology 92.4 (2018): 1639-1655. https://doi.org/10.1007/s00204-018-2160-9

The article indicates that both PhIP and ethanol produced by consuming processed meat can induce cytotoxicity in breast cells. PhIP enhances DNA damage by activating the CYP1B1 and ER-α pathways, while ethanol synergistically intensifies the genotoxic effect of PhIP through oxidative stress, especially in ER-α -positive cells, thereby increasing the risk of breast cancer.

2. Zapico Linares, Aida, et al. "Potential of Fiber and Probiotics to Fight Against the Effects of PhIP+ DSS-Induced Carcinogenic Process of the Large Intestine." American Chemical Society 72(45): 25161–25172 (2024). https://doi.org/10.1021/acs.jafc.4c07366

Studies have shown that dietary fiber and probiotics can alleviate colonic mucosal injury in rats induced by the combination of PhIP and DSS. Fiber supplementation reduces crypt loss and inflammation, while probiotics increase colon length. Both regulate the intestinal flora and reduce the abundance of pro-inflammatory bacteria, thereby countering the intestinal toxicity of PhIP.

3. Griggs, Amy M., et al. "2-Amino-1-methyl-6-phenylimidazo [4, 5-b] pyridine (PhIP) is selectively toxic to primary dopaminergic neurons in vitro." Toxicological Sciences 140.1 (2014): 179-189. https://doi.org/10.1093/toxsci/kfu060

Studies have found that PhIP and its metabolite N-OH-PhIP produced by dietary processing have selective toxicity to dopaminergic neurons, which can lead to neuronal reduction and oxidative damage. However, blueberry extract can effectively alleviate its neurotoxic effects through antioxidant mechanisms.

4. Akhtar, Shabana, et al. "Ex vivo/in vitro protective effect of myricetin bulk and nano-forms on PhIP-induced DNA damage in lymphocytes from healthy individuals and pre-cancerous MGUS patients." Archives of Toxicology 94.7 (2020): 2349-2357. https://doi.org/10.1007/s00204-020-02754-x

Research has found that the dietary mutagen PhIP can induce DNA damage in lymphocytes. The flavonoid myxidine, especially its nanoform, can significantly inhibit DNA strand breaks and micronucleus formation caused by PhIP, and has a better protective effect on lymphocytes in patients with precancerous lesions. The mechanism may be related to the regulation of gene pathways such as P53.

5. Yeh, I-Jeng, et al. "6-Shogaol suppresses 2-amino-1-methyl-6-phenylimidazo [4, 5-b] pyridine (PhIP)-induced human 786-O renal cell carcinoma osteoclastogenic activity and metastatic potential." Nutrients 11.10 (2019): 2306. https://doi.org/10.3390/nu11102306

Research has found that the dietary carcinogen PhIP can promote the secretion of PTHrP by renal cancer cells, thereby regulating the bone microenvironment, enhancing the activity of osteoclasts, and leading to bone metastasis. The active component 6-gingerol of ginger can effectively inhibit PHIP-mediated bone resorption.

Creative Biolabs: PHIP Antibodies for Research

Creative Biolabs specializes in the production of high-quality PHIP antibodies for research and industrial applications. Our portfolio includes monoclonal antibodies tailored for ELISA, Flow Cytometry, Western blot, immunohistochemistry, and other diagnostic methodologies.

• Custom Myoglobin Antibody Development: Tailor-made solutions to meet specific research requirements.
• Bulk Production: Large-scale antibody manufacturing for industry partners.
• Technical Support: Expert consultation for protocol optimization and troubleshooting.
• Aliquoting Services: Conveniently sized aliquots for long-term storage and consistent experimental outcomes.

For more details on our PHIP antibodies, custom preparations, or technical support, contact us at email.