P80 form of the human tumor necrosis factor receptor is involved in DNA fragmentation

M Higuchi1, B B Aggarwal

  • 1Department of Clinical Immunology and Biological Therapy, University of Texas M.D. Anderson Cancer Center, Houston 77030.

FEBS Letters
|October 4, 1993
PubMed

Insights

Tumor necrosis factor (TNF) receptors, p60 and p80, mediate DNA fragmentation in tumor cells. The p80 receptor specifically appears crucial for TNF-induced DNA fragmentation, as its regeneration correlates with the reappearance of this effect.

Area of Science:

  • Molecular Biology
  • Immunology
  • Cell Biology

Background:

  • Two types of Tumor Necrosis Factor (TNF) receptors, p60 and p80, have been identified.
  • TNF is known to induce DNA fragmentation in specific tumor cell lines, but the roles of p60 and p80 are unclear.

Purpose of the Study:

  • To investigate the specific roles of the p60 and p80 TNF receptors in TNF-induced DNA fragmentation.

Main Methods:

  • U-937 cells were treated with phorbol ester to downregulate TNF receptors.
  • Receptor regeneration and TNF-induced DNA fragmentation were monitored after phorbol ester removal.

Main Results:

  • Phorbol ester treatment downregulated both p60 and p80 TNF receptors, abolishing TNF-induced DNA fragmentation.
  • Upon phorbol ester removal, p80 receptors regenerated rapidly, coinciding with the reappearance of TNF-induced DNA fragmentation.
  • The p60 receptor form did not show similar regeneration patterns.

Conclusions:

  • The p80 TNF receptor is suggested to be the primary mediator of TNF-induced DNA fragmentation.
  • These findings highlight the differential roles of TNF receptor subtypes in cellular responses.

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