Related Experiment Video

Updated: Dec 20, 2025

Analysis of the c-KIT Ligand Promoter Using Chromatin Immunoprecipitation
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Analysis of the c-KIT Ligand Promoter Using Chromatin Immunoprecipitation

Published on: June 27, 2017

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Small Molecule Intervention in a Protein Kinase C-Gli Transcription Factor Axis

UyenPhuong Tran1, Grace C Zhang2, Ryan Eom3

  • 1Department of Chemistry and Biochemistry, California State University Fullerton, 800 N State College Blvd, Fullerton, California 92831, United States.

ACS Chemical Biology
|June 2, 2020
PubMed

Insights

Aberrations in the Hedgehog (Hh) signaling pathway drive many cancers. Researchers identified a novel protein kinase C (PKC) effector that inhibits Gli transcription factors downstream of Smo, offering new therapeutic strategies for Hh-driven cancers.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Aberrant Hedgehog (Hh) signaling is implicated in numerous human cancers.
  • A subset of these cancers are resistant to Smoothened (Smo)-targeting therapies, necessitating novel therapeutic targets.
  • A link between Hh pathway transcription factors (Gli) and protein kinase C (PKC) isozymes has been recently discovered.

Purpose of the Study:

  • To investigate the influence of structurally diverse PKC effectors on Gli function.
  • To identify novel agents that can inhibit Gli activity downstream of Smo.
  • To explore new therapeutic avenues for Hh pathway-dependent cancers.

Main Methods:

  • Screening of a diverse library of PKC effectors.
  • Utilizing cell lines with distinct Gli activation mechanisms (upstream and downstream of Smo).
  • Assessing the inhibitory effect of PKC effectors on Gli function.

Main Results:

  • A novel PKC effector was identified as a potent Gli antagonist.
  • This antagonist functions downstream of Smo via a MEK-independent mechanism.
  • The identified agent exhibits nanomolar potency in inhibiting Gli activity.

Conclusions:

  • A PKC effector acts as a nanomolar Gli antagonist downstream of Smo.
  • This discovery provides a new tool to study PKC-Hh pathway crosstalk.
  • It opens new therapeutic opportunities for Smo-insensitive Hh-driven cancers.

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