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The Hh pathway promotes cell apoptosis through Ci-Rdx-Diap1 axis
Bin Liu1, Yan Ding1, Bing Sun2
1College of Life Sciences, Shandong Agricultural University, Tai'an, China.
Cell Death Discovery
|September 25, 2021
Summary
The Hedgehog (Hh) pathway promotes apoptosis by targeting Diap1 via the E3 ubiquitin ligase Rdx. This finding reveals a new role for the Hh pathway in cell death, impacting cancer treatment strategies.
Area of Science:
- Cell Biology
- Molecular Biology
- Developmental Biology
Background:
- Apoptosis is a critical cellular process for development and disease prevention, but its regulation is not fully understood.
- Deregulation of apoptosis is implicated in birth defects and various human diseases, highlighting the need for further research into its mechanisms.
Purpose of the Study:
- To identify novel components involved in the regulation of apoptosis.
- To investigate the role of the Hedgehog (Hh) signaling pathway in apoptosis.
- To elucidate the molecular mechanisms by which the Hh pathway influences apoptosis.
Main Methods:
- Conducted a modifier screen to identify genetic factors affecting apoptosis.
- Utilized molecular biology techniques to analyze gene expression and protein interactions.
- Investigated the physical binding and ubiquitination status of key apoptotic regulators.
Main Results:
- The Hedgehog (Hh) pathway was found to aggravate Hid-induced apoptosis.
- The Hh pathway triggers apoptosis through its transcriptional target gene, rdx, which encodes an E3 ubiquitin ligase.
- Rdx promotes K63-linked polyubiquitination of Diap1, attenuating the Diap1-Dronc interaction without affecting Diap1 stability.
Conclusions:
- The oncogenic Hh pathway unexpectedly promotes apoptosis via the Ci-Rdx-Diap1 module.
- This discovery uncovers a novel mechanism linking the Hh pathway to programmed cell death.
- The findings raise concerns regarding the use of Hh pathway inhibitors as anti-tumor drugs due to their potential to promote apoptosis.
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