Cytometry Research Uncovers Tumor Suppressor Gene-ECRG4 Interaction with Innate Immunity Receptor Complex

Strategic Insights -

Research on cytometry has led to a discovery that the human c2orf40 gene encodes a tumor suppressor gene called esophageal cancer-related gene-4 (ECRG4), which interacts with the innate immunity receptor complex. According to a study published in Inflammation Research, ECRG4 has pro- and anti-inflammatory activities that depend on cell surface processing. The study, conducted by researchers from the University of California, found that ECRG4 interacts with the TLR4-MD2-CD14 receptor complex on human granulocytes, leading to the internalization of the C-terminal 16 amino acid domain of ECRG4, ECRG4(133-148), through non-canonical NF kappa B signal transduction.

Key Takeaways:

  • The human c2orf40 gene encodes a tumor suppressor gene called esophageal cancer-related gene-4 (ECRG4) with pro- and anti-inflammatory activities that depend on cell surface processing.
  • Interactions between ECRG4 and the innate immunity receptor complex were assessed by flow cytometry, immunohistochemistry, confocal microscopy, and co-immunoprecipitation.
  • Phage display was used for ligand targeting to cells that overexpress the TLR4-MD2-CD14, demonstrating a physical interaction between ECRG4 and TLR4-MD2-CD14 on human granulocytes.
  • Flow cytometry shows ECRG4 on the cell surface of a subset of CD14(+) and CD16(+) leukocytes.
  • The C-terminal 16 amino acid domain of ECRG4 (ECRG4(133-148)) appears to be processed and shed in a cohort of trauma patients.
  • Phage targeting the putative ligand shows that the peptide sequence internalizes into cells through the TLR4/CD14/MD2 complex, but modulates inflammation through non-canonical NF kappa B signal transduction.
  • ECRG4 is present on the surface of human monocytes and granulocytes.

Statistics:

  • In a cohort of trauma patients, the C-terminal 16 amino acid domain of ECRG4 (ECRG4(133-148)) is processed and shed, presumably at a thrombin-like consensus sequence.
  • Phage targeting this putative ligand shows that the peptide sequence internalizes into cells through the TLR4/CD14/MD2 complex, modulating inflammation through non-canonical NF kappa B signal transduction.
  • Flow cytometry shows ECRG4 on the cell surface of a subset of CD14(+) and CD16(+) leukocytes.

Sources:

  • Esophageal cancer-related gene-4 (ECRG4) interactions with the innate immunity receptor complex. Inflammation Research, 2015;64(2):107-118.
  • Springer Basel Ag, Picassoplatz 4, Basel, 4052, Switzerland. (Springer - www.springer.com; Inflammation Research - www.springerlink.com/content/1023-3830/)
  • S. Podvin, University of California, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093, United States.