Related Experiment Video
Updated: Aug 16, 2026

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway
Published on: August 23, 2024
Inhibition of apoptosis by Nur77 through NF-kappaB activity modulation
11INRS-Institut Armand-Frappier, Laval, QC, Canada.
Abstract:
The orphan nuclear receptor Nur77 has been described as a mediator of apoptosis and has also been associated with growth promotion and apoptotic resistance. This study aimed at evaluating the contribution of Nur77 to different apoptotic stimuli. Nur77 overexpression in the fibroblastic cell line HEK293 promoted resistance to programmed cell death induced by death receptor engagement, DNA-damaging agents and endoplasmic reticulum stress. Nur77 overexpression led to enhanced NF-kappaB activity, and DNA-binding inhibitors confirmed the contribution of NF-kappaB to Nur77 antiapoptotic activity. Nur77 overexpression leads to NF-kappaB-dependent induction of the antiapoptotic gene cIAP1. Paradoxically, while dominant-negative Nur77 expression sensitised cells to Fas ligand-induced cell death, it protected cells from endoplasmic reticulum stress apoptosis in a manner similar to wild-type Nur77. These results show that nuclear crosstalk between Nur77 and other transcription factors contribute to cell fate in response to different apoptosis-inducing agents.
Insights
The orphan nuclear receptor Nur77 enhances cell survival by resisting apoptosis through NF-kappaB signaling. This study reveals Nur77
Area of Science:
- Molecular Biology
- Cell Biology
- Cancer Research
Background:
- The orphan nuclear receptor Nur77 plays a complex role in cell fate, with reported associations with both apoptosis promotion and resistance.
- Understanding Nur77's precise function under various apoptotic stimuli is crucial for its therapeutic potential.
Purpose of the Study:
- To investigate the specific role of Nur77 in mediating cellular responses to diverse apoptotic triggers.
- To elucidate the molecular mechanisms underlying Nur77's influence on programmed cell death.
Main Methods:
- Overexpression of Nur77 in HEK293 cells.
- Induction of apoptosis using death receptor ligands, DNA-damaging agents, and endoplasmic reticulum stress.
- Assessment of NF-kappaB activity and cIAP1 gene expression.
- Use of dominant-negative Nur77 and DNA-binding inhibitors.
Main Results:
- Nur77 overexpression conferred resistance to apoptosis induced by multiple stimuli.
- Nur77 enhanced NF-kappaB activity, which was essential for its antiapoptotic effects, including the induction of cIAP1.
- Dominant-negative Nur77 sensitized cells to death receptor-mediated apoptosis but protected against ER stress-induced apoptosis.
Conclusions:
- Nur77 acts as a key regulator of apoptosis, promoting cell survival through NF-kappaB-dependent pathways.
- The context-dependent effects of Nur77 highlight intricate nuclear crosstalk influencing cell fate decisions.
- Nur77's dual role in apoptosis modulation offers insights into targeted cancer therapies.
More Related Videos
Related Concept Videos
The Intrinsic Apoptotic Pathway
Abnormal Proliferation
NF-κB-dependent Signaling Pathway
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
Inhibition of Cdk Activity
Inhibition of CDK Activity
The Extrinsic Apoptotic Pathway

