Characterization of RNF175, A Novel Ring Finger E3 Ligase
Date
2023-05
Authors
Perez Espinosa, Jennifer
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Abstract
RING finger (RNF) proteins are a class of E3 ligases involved in processes such as cell division, interferon signaling, proinflammatory pathways, and growth factor signaling to name a few. Although many RNF isoforms have been characterized and associated with their respective functions, RNF175 has yet to be characterized and its regulatory mechanisms remain undefined. In this study we elucidate the characterization and associated pathways of RNF175. However, of the E3 ligase family, RNF121 shares close homology to RNF175. We hypothesize that RNF175 will resemble characteristics and mechanisms like RNF121. Using The Cancer Genome Atlas (TCGA) Genome Data Analysis Center (GDAC), RNF175 is a differentially expressed RING finger protein in glioma cancer cells and high expression of this gene is associated with low survivability of glioma patients. Using bioinformatics, we show, many transcription factor binding sites were found to be prominent in the promoter of this gene, including GR𝛽/𝛼, FOXA1, AP-2𝛼, and C/EBP. These transcription factors are known to regulate inflammatory responses, cell division, chromatin remodeling, and cell differentiation. Different protein motifs were identified, one being the FYVE motif which binds to PI3P, a phospholipid protein involved in the AKT survival pathway. In addition to the zinc finger binding domain the protein contains 5 transmembrane regions. Microarray shows differential expression of RNF175 in MCF10A human mammary epithelial cell line, upregulation in neutrophil cells during inflammatory responses and high expression in the brain. These data show RNF175 interactions with the AKT, ERAD pathway, and cytoskeletal proteins as their protein binding partners. Additional studies will need to confirm if RNF175 is of clinical significance for a diagnostic marker and its role in glioma cancers.
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Keywords
bioinformatics, E3, ligase, ubiquitination, Alzheimer's, glioma, inflammation, neuroinflammation
Citation
Perez Espinosa, J. (2023). Characterization of RNF175, a novel ring finger E3 ligase. Honors College, Texas State University.