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Updated: Dec 12, 2025

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
08:49

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries

Published on: January 22, 2019

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Tristetraprolin Posttranscriptionally Downregulates TRAIL Death Receptors

Won Hyeok Lee1,2, Myung Woul Han1,2, Song Hee Kim1,2

  • 1Department of Otorhinolaryngology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 44033, Korea.

Cells
|August 14, 2020
PubMed

Insights

Tristetraprolin (TTP) regulates cancer cell sensitivity to Tumor Necrosis Factor (TNF)-related apoptosis-inducing ligand (TRAIL) therapy. TTP controls the stability of TRAIL death receptor (DR) mRNA, impacting treatment response.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Immunology

Background:

  • Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) shows promise for cancer therapy but faces resistance in many primary cancers.
  • The mechanisms underlying TRAIL resistance, particularly concerning death receptor (DR) mRNA stability, remain incompletely understood.

Purpose of the Study:

  • To elucidate the molecular mechanisms controlling TRAIL death receptor (DR) mRNA stability.
  • To investigate the role of tristetraprolin (TTP) in regulating TRAIL sensitivity in cancer cells.

Main Methods:

  • Analysis of AU-rich elements (AREs) in the 3'-untranslated regions (3'-UTRs) of DR4 and DR5 mRNA.
  • Assessment of TTP binding to AREs and its effect on DR4/5 mRNA decay.
  • Evaluation of TTP's impact on TRAIL sensitivity in colon cancer cells through overexpression and down-regulation studies.

Main Results:

  • Tristetraprolin (TTP), an ARE-binding protein, binds to multiple AREs in the 3'-UTRs of DR4 and DR5 mRNA, enhancing their decay.
  • TTP overexpression confers TRAIL resistance in colon cancer cells by reducing DR4/5 expression.
  • Down-regulation of TTP increases TRAIL sensitivity by upregulating DR4/5 expression.

Conclusions:

  • TTP plays a critical role in posttranscriptional regulation of TRAIL death receptors, influencing TRAIL sensitivity in cancer.
  • TTP status may serve as a predictive biomarker for TRAIL-based cancer treatments.
Keywords:
AU-rich elementscancer treatmentdeath receptorposttranscriptional modificationtristetraprolintumor necrosis factor-related apoptosis-inducing ligand

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