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Published on: March 24, 2023
Casting the Caspase Activity and Apoptosis Inhibitor 1 Phosphoregulation Through Global Phosphoproteomes
Pathiyil Sajini Sekhar1, Amal Fahma1, Athira Perunally Gopalakrishnan1
1Centre for Integrative Omics Data Science (CIODS), Yenepoya (Deemed to be University), Mangalore, India.
Abstract:
Caspase Activity and Apoptosis Inhibitor 1 (CAAP1) is a regulatory protein known to suppress apoptosis and support cell survival with implications in cancer progression, cell migration, and angiogenesis, yet its regulation at the post-transcriptional level remains poorly understood and is underexplored as a therapeutic target. This study aimed to investigate CAAP1 phosphorylation and its functional significance using global phosphoproteomic datasets. We systematically analyzed 885 human phosphoproteomic profiling and 172 differential expression datasets to identify Class 1 phosphorylation sites (PS) in CAAP1. Co-regulated protein phosphosites were examined to explore CAAP1's biological roles, and enrichment analysis was performed. The four PS, S203, S89, S312, and T90, were the predominantly detected sites. Our results reveal that the PS co-regulated with CAAP1 predominant sites were enriched in splicing-related processes, with strong associations with spliceosome-related proteins and apoptotic regulators. This phosphosite-centric study suggests that CAAP1 phosphoregulatory network is involved in splicing mechanisms, apoptosis regulation, and cancer progression. The study positions CAAP1 phosphorylation in processes frequently dysregulated in cancer and provides a foundation for future translational studies aimed at targeting CAAP1 phosphoregulation as a therapeutic strategy.
Insights
Caspase Activity and Apoptosis Inhibitor 1 (CAAP1) phosphorylation, particularly at sites S203, S89, S312, and T90, is linked to splicing and apoptosis. This CAAP1 phosphoregulatory network offers potential therapeutic targets for cancer.
Area of Science:
- Molecular Biology
- Cancer Research
- Proteomics
Background:
- Caspase Activity and Apoptosis Inhibitor 1 (CAAP1) is a protein that inhibits apoptosis and promotes cell survival.
- CAAP1's role in cancer progression, migration, and angiogenesis is recognized, but its post-transcriptional regulation, specifically phosphorylation, is not well understood.
- CAAP1 is an underexplored therapeutic target for cancer treatment.
Purpose of the Study:
- To investigate the phosphorylation of CAAP1 and its functional significance.
- To identify key phosphorylation sites (PS) on CAAP1 using global phosphoproteomic data.
- To explore the biological roles of CAAP1 through co-regulated phosphosites.
Main Methods:
- Systematic analysis of 885 human phosphoproteomic profiling datasets.
- Analysis of 172 differential expression datasets.
- Identification of Class 1 phosphorylation sites (PS) in CAAP1.
- Examination of co-regulated protein phosphosites and enrichment analysis.
Main Results:
- Four predominant CAAP1 phosphorylation sites were identified: S203, S89, S312, and T90.
- Co-regulated phosphosites associated with CAAP1's predominant sites were enriched in splicing-related processes.
- Strong associations were found between these phosphosites, spliceosome-related proteins, and apoptotic regulators.
Conclusions:
- The CAAP1 phosphoregulatory network is implicated in splicing mechanisms, apoptosis regulation, and cancer progression.
- CAAP1 phosphorylation occurs in cellular processes frequently dysregulated in cancer.
- This study provides a basis for developing therapeutic strategies targeting CAAP1 phosphoregulation in cancer.
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