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<p>The Tumour Protein D52 (TPD52) family, including TPD52, TPD52L1, and TPD52L2, plays critical roles in membrane trafficking, lipid metabolism, and oncogenic signalling, with its overexpression linked to multiple cancers. Phosphorylation is a key regulator of their functions, yet their phosphoproteomic landscape remains underexplored. This study integrates over 3,825 public human phosphoproteomic datasets to map phosphorylation profiles of TPD52, TPD52L1, and TPD52L2, identifying dominant phosphosites like S171, S176, S149, and S12, S166 within conserved coiled-coil and PEST-like domains. CAMK2D was identified as a predominant shared kinase, alongside CDK2 and GRK5, associating these modifications with calcium signaling, cell cycle progression, and cytoskeletal remodeling. Co-phosphoregulation highlighted positive interactions with ABRAXAS2 and negative correlations with ABLIM3, implicating involvement in ubiquitin-mediated degradation, epithelial-mesenchymal transition (EMT), and cytokinesis. Notably, hypophosphorylation at TPD52_S171/S176 was observed in hepatocellular and lung carcinomas, whereas hyperphosphorylation at TPD52L2_S166 prevailed in ovarian and pancreatic cancers, underscoring biomarker utility. Phosphorylation-driven interactomes emphasized roles in vesicular trafficking and oncogenesis This study catalogues the phosphorylation events and explores the potential of TPD52 family as a phosphoregulated hub in cancer biology, with CAMK2D as a potential therapeutic target.</p>

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Integrative phosphoproteomic network analysis identifies CAMK2D as a shared regulator of TPD52 family proteins in cancer

  • 期刊论文

  • 发表日期：

    2025年12月9日

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  • Noreen A. Khan,
  • Amal Fahma,
  • Althaf Mahin,
  • Athira Perunelly Gopalakrishnan,
  • Prathik Basthikoppa Shivamurthy,
  • Athira C. Rajeev,
  • Rajesh Raju

摘要

The Tumour Protein D52 (TPD52) family, including TPD52, TPD52L1, and TPD52L2, plays critical roles in membrane trafficking, lipid metabolism, and oncogenic signalling, with its overexpression linked to multiple cancers. Phosphorylation is a key regulator of their functions, yet their phosphoproteomic landscape remains underexplored. This study integrates over 3,825 public human phosphoproteomic datasets to map phosphorylation profiles of TPD52, TPD52L1, and TPD52L2, identifying dominant phosphosites like S171, S176, S149, and S12, S166 within conserved coiled-coil and PEST-like domains. CAMK2D was identified as a predominant shared kinase, alongside CDK2 and GRK5, associating these modifications with calcium signaling, cell cycle progression, and cytoskeletal remodeling. Co-phosphoregulation highlighted positive interactions with ABRAXAS2 and negative correlations with ABLIM3, implicating involvement in ubiquitin-mediated degradation, epithelial-mesenchymal transition (EMT), and cytokinesis. Notably, hypophosphorylation at TPD52_S171/S176 was observed in hepatocellular and lung carcinomas, whereas hyperphosphorylation at TPD52L2_S166 prevailed in ovarian and pancreatic cancers, underscoring biomarker utility. Phosphorylation-driven interactomes emphasized roles in vesicular trafficking and oncogenesis This study catalogues the phosphorylation events and explores the potential of TPD52 family as a phosphoregulated hub in cancer biology, with CAMK2D as a potential therapeutic target.