Bcl-2-associated transcription factor 1 Ser290 phosphorylation mediates DNA damage response and regulates

Jia Liu1, Jingyi Li2, Zhao Sun2

  • 1Key Laboratory for Experimental Teratology of the Ministry of Education, Cancer Research Center, and Department of Cell Biology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, China.

Abstract

Insights

Researchers identified a key protein phosphorylation in gastric cancer linked to DNA damage and radiotherapy resistance. This finding highlights BCLAF1 phosphorylation as a potential therapeutic target for improving cancer treatment outcomes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • DNA damage response is crucial in cancer development and resistance to radiotherapy.
  • Protein phosphorylation regulates DNA damage response, but key mediators in gastric cancer radiosensitivity require further investigation.

Purpose of the Study:

  • To identify key phosphoproteins involved in gastric cancer radiosensitivity.
  • To explore the role of specific protein phosphorylation in DNA damage response and patient prognosis.

Main Methods:

  • Label-free phosphoproteomics and high-resolution mass spectrometry were used on gastric cancer tissues.
  • Dysregulated phosphoproteins and pathways were analyzed using Gene Set Enrichment Analysis (GSEA).
  • Specific phosphorylation sites were validated using antibodies and functional/clinical approaches.

Main Results:

  • Identified 832 unique phosphorylated sites, with significant enrichment in DNA-damage-response pathways.
  • Found upregulation of Bcl-2-associated transcription factor 1 (BCLAF1) phosphorylation at Ser290 (pBCLAF1 (Ser290)) in tumors.
  • pBCLAF1 (Ser290) upregulation correlated with poor prognosis, suppressed GC cell proliferation, and enhanced DNA repair, inhibiting apoptosis after irradiation.

Conclusions:

  • BCLAF1 phosphorylation at Ser290 is implicated in regulating DNA damage response in gastric cancer.
  • pBCLAF1 (Ser290) represents a potential therapeutic target for overcoming radiotherapy resistance in gastric cancer.

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