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P80 form of the human tumor necrosis factor receptor is involved in DNA fragmentation
1Department of Clinical Immunology and Biological Therapy, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Abstract:
Two different types of TNF receptors with molecular masses of 60 kDa (p60) and 80 kDa (p80) have been identified. TNF is known to cause DNA fragmentation in certain tumor cell lines but the role of p60 and p80 in this action is not understood. In the present study, we examined the role of these receptors in TNF-induced DNA fragmentation. Treatment of U-937 cells with phorbol ester caused downregulation of both types of TNF receptors and this was accompanied by disappearance of the TNF-induced DNA fragmentation. The removal of phorbol ester led to two time-dependent events: (1) the rapid regeneration of the p80 form but not the p60 form of the TNF receptor; and (2) the reappearance of TNF-induced DNA fragmentation. These results suggest that the p80 receptor could mediate the TNF-induced DNA fragmentation.
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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