Related Experiment Video
Updated: Dec 25, 2025
Author Spotlight: Exploring the Role of FAM83A in Cervical Cancer
Published on: February 9, 2024
Pro-apoptotic functions of TRAF2 in p53-mediated apoptosis induced by cisplatin
Mei Tsuchida1, Takumi Yokosawa1, Takuya Noguchi1
1Laboratory of Health Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University.
Abstract:
Tumor necrosis factor receptor-associated factor 2 (TRAF2) is an essential component of tumor necrosis factor-α (TNF-α) signaling that regulates nuclear factor-κB (NF-κB) and c-Jun N-terminal kinase (JNK) pathways, and compelling evidence has demonstrated that TRAF2 suppresses TNF-α-induced cytotoxicity. On the other hand, it has been reported that oxidative stress-induced cytotoxicity is potentiated by TRAF2, indicating that TRAF2 both positively and negatively regulates stress-induced cytotoxicity in a context-specific manner. However, the causal role of TRAF2 in DNA damage response (DDR) remains to be explored. In this study, we assessed the function of TRAF2 in DDR induced by cisplatin, a representative DNA-damaging agent, and found that TRAF2 exerts pro-apoptotic activity through p53-dependent mechanisms at least in human fibrosarcoma cell line HT1080. TRAF2 deficient cells exhibit significant resistance to cell death induced by cisplatin, accompanied by the reduction of both p53 protein level and caspase-3 activation. Moreover, cisplatin-induced JNK activation was attenuated in TRAF2-deficient cells, and pharmacological inhibition of JNK signaling suppressed p53 stabilization. These results suggest that TRAF2 promotes p53-dependent apoptosis by activating the JNK signaling cascade in HT1080 cells. Thus, our data demonstrate a novel function of TRAF2 in cisplatin-induced DDR as a pro-apoptotic protein.
Insights
Tumor necrosis factor receptor-associated factor 2 (TRAF2) promotes cancer cell death after DNA damage. TRAF2 activates p53 and JNK pathways, making cells sensitive to cisplatin treatment.
Area of Science:
- Cellular and Molecular Biology
- Cancer Research
- Signal Transduction
Background:
- Tumor necrosis factor receptor-associated factor 2 (TRAF2) plays a dual role in regulating cytotoxicity, suppressing TNF-α-induced cell death but potentiating oxidative stress-induced cell death.
- The specific role of TRAF2 in the DNA damage response (DDR) pathway remains largely uncharacterized.
Purpose of the Study:
- To investigate the function of TRAF2 in the DNA damage response (DDR) induced by cisplatin.
- To elucidate the molecular mechanisms underlying TRAF2's role in cisplatin-induced apoptosis.
Main Methods:
- Utilized the human fibrosarcoma cell line HT1080.
- Assessed the impact of TRAF2 deficiency on cisplatin-induced cell death, p53 levels, caspase-3 activation, and JNK signaling.
- Employed pharmacological inhibition of JNK signaling.
Main Results:
- TRAF2 deficiency significantly enhanced resistance to cisplatin-induced cell death in HT1080 cells.
- TRAF2-deficient cells showed reduced p53 protein levels and caspase-3 activation following cisplatin treatment.
- Cisplatin-induced JNK activation was diminished in TRAF2-deficient cells, and JNK inhibition reduced p53 stabilization.
Conclusions:
- TRAF2 acts as a pro-apoptotic protein in the DNA damage response to cisplatin.
- TRAF2 promotes p53-dependent apoptosis by activating the JNK signaling cascade in HT1080 cells.
- This study reveals a novel function for TRAF2 in mediating sensitivity to DNA-damaging agents.
More Related Videos
19:44Enhancement of Apoptotic and Autophagic Induction by a Novel Synthetic C-1 Analogue of 7-deoxypancratistatin in Human Breast Adenocarcinoma and Neuroblastoma Cells with Tamoxifen
Published on: May 30, 2012
15:43Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes
Published on: January 7, 2013
Related Concept Videos
01:31The Intrinsic Apoptotic Pathway
02:23Abnormal Proliferation
02:36DNA Damage can Stall the Cell Cycle
02:36DNA Damage Can Stall the Cell Cycle
01:17The Extrinsic Apoptotic Pathway
01:19Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...