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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
PubMed

Insights

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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