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Strategic Screening and Characterization of the Visual GPCR-mini-G Protein Signaling Complex for Successful Crystallization
Published on: March 16, 2020
Cloning and characterization of the canine receptor for advanced glycation end products
Hugo Murua Escobar1, Jan T Soller, Katharina A Sterenczak
1Small Animal Clinic, University of Veterinary Medicine, Bischofsholer Damm 15, D-30173 Hannover, Germany. escobar@uni-bremen.de
Abstract:
Metastasis is one of the major problems when dealing with malignant neoplasias. Accordingly, the finding of molecular targets, which can be addressed to reduce tumour metastasising, will have significant impact on the development of new therapeutic approaches. Recently, the receptor for advanced glycation end products (RAGE)-high mobility group B1 (HMGB1) protein complex has been shown to have significant influence on invasiveness, growth and motility of tumour cells, which are essential characteristics required for metastatic behaviour. A set of in vitro and in vivo approaches showed that blocking of this complex resulted in drastic suppression of tumour cell growth. Due to the similarities of human and canine cancer the dog has joined the common rodent animal model for therapeutic and preclinical studies. However, complete characterisation of the protein complex is a precondition to a therapeutic approach based on the blocking of the RAGE-HMGB1 complex to spontaneously occurring tumours in dogs. We recently characterised the canine HMGB1 gene and protein completely. Here we present the complete characterisation of the canine RAGE gene including its 1384 bp mRNA, the 1215 bp protein coding sequence, the 2835 bp genomic structure, chromosomal localisation, gene expression pattern, and its 404 amino acid protein. Furthermore we compared the CDS of six different canine breeds and screened them for single nucleotide polymorphisms.
Insights
Researchers fully characterized the canine receptor for advanced glycation end products (RAGE) gene. This is a crucial step toward developing new cancer therapies targeting the RAGE-high mobility group B1 (HMGB1) protein complex in dogs.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Metastasis is a significant challenge in cancer treatment, necessitating the identification of molecular targets to inhibit tumor spread.
- The receptor for advanced glycation end products (RAGE)-high mobility group B1 (HMGB1) protein complex plays a key role in tumor cell invasiveness, growth, and motility, essential for metastasis.
- Blocking this complex has shown promise in suppressing tumor growth in preclinical studies.
Purpose of the Study:
- To fully characterize the canine RAGE gene, including its mRNA, protein-coding sequence, genomic structure, chromosomal localization, and expression pattern.
- To provide a comprehensive understanding of canine RAGE as a prerequisite for developing targeted therapies against the RAGE-HMGB1 complex in canine cancers.
- To compare the coding sequences (CDS) of canine RAGE across different breeds and identify single nucleotide polymorphisms (SNPs).
Main Methods:
- Bioinformatic analysis of canine RAGE gene sequences (mRNA, protein-coding, genomic).
- Determination of chromosomal localization and gene expression patterns.
- Comparative analysis of CDS from six different canine breeds, including SNP screening.
Main Results:
- Complete characterization of the canine RAGE gene, including its 1384 bp mRNA, 1215 bp protein-coding sequence, 2835 bp genomic structure, and chromosomal localization.
- Identification and characterization of the 404 amino acid canine RAGE protein.
- Comparative analysis revealed variations in the CDS across different canine breeds, with identified single nucleotide polymorphisms.
Conclusions:
- The comprehensive characterization of the canine RAGE gene and protein provides essential foundational data for future therapeutic strategies.
- Targeting the RAGE-HMGB1 complex represents a promising avenue for developing novel anti-metastatic therapies in canine oncology.
- Understanding genetic variations in canine RAGE across breeds may inform personalized therapeutic approaches.
