Towards the construction of an interactome for Human WD40 protein family
Hulikal Shivashankara Santosh Kumar1, Vadlapudi Kumar2, Sharath Pattar3
1Department of Biotechnology and Bioinformatics, Kuvempu University, Shankaraghatta - 577451, Karnataka, India.
Abstract:
WD40 proteins are involved in a variety of protein-protein interactions as part of a multi-protein assembly modulating diverse and critical cellular process. It is known that several proteins of this family have been implicated in different disorders such as developmental abnormalities and cancer. However, molecular functions of many proteins in this family are yet unknown and it is of clinical interest. Therefore, it is of interest to define, construct, understand, analyze, evaluate, redefine and refine an interactome for WD40 protein family. We used data from literature mining using Cytoscape followed by linear regression analysis between Betweenness centrality and stress scores to define a model to filter the nodes in a representative WD40 interactome construction. We identified 10 ranked nodes in this analysis and subsequent microarray data selected three of them in insulin resistance that is further demonstrated in HepG2 cell culture models. We also observed the expression of GRWD1, RBBP5 and WDR5 genes during perturbation. Thus, we report hub nodes of WD40 interactome in insulin resistance. It should be noted that the pipeline using protein interaction network help find new proteins of clinical importance.
Insights
This study identifies key WD40 protein interactions linked to insulin resistance. The findings highlight novel proteins with potential clinical significance in metabolic disorders.
Area of Science:
- Biochemistry and Molecular Biology
- Systems Biology
- Genomics
Background:
- WD40 proteins are crucial for cellular processes, participating in diverse protein-protein interactions within multi-protein complexes.
- Dysregulation of WD40 proteins is associated with various diseases, including developmental abnormalities and cancer, yet their specific molecular functions remain largely unelucidated.
- Understanding the WD40 protein interactome is vital for identifying novel therapeutic targets and understanding disease mechanisms.
Purpose of the Study:
- To construct and refine a comprehensive WD40 protein interactome.
- To identify key WD40 proteins and their interactions relevant to insulin resistance.
- To establish a computational pipeline for discovering clinically significant proteins within protein interaction networks.
Main Methods:
- Literature mining and network construction using Cytoscape.
- Linear regression analysis of Betweenness centrality and stress scores to filter network nodes.
- Microarray data analysis and validation in HepG2 cell culture models to identify hub nodes in insulin resistance.
Main Results:
- A representative WD40 interactome was constructed, identifying 10 ranked nodes.
- Three specific WD40 proteins (GRWD1, RBBP5, WDR5) were identified as hub nodes associated with insulin resistance.
- Gene expression of GRWD1, RBBP5, and WDR5 was observed during cellular perturbation, confirming their role in insulin resistance models.
Conclusions:
- The study successfully defined a WD40 protein interactome and identified critical hub nodes involved in insulin resistance.
- The developed computational pipeline demonstrates the utility of protein interaction network analysis for discovering novel proteins of clinical importance.
- These findings provide a foundation for further research into the role of specific WD40 proteins in metabolic diseases and potential therapeutic interventions.
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