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Updated: Aug 11, 2026

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter
11:32

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter

Published on: March 27, 2020

Activating transcription factor 3, a stress-inducible gene, suppresses Ras-stimulated tumorigenesis

Dan Lu1, Curt D Wolfgang, Tsonwin Hai

  • 1Ohio State Biochemistry Program, Department of Molecular and Cellular Biochemistry and Center for Molecular Neurobiology, Ohio State University, Columbus, OH 43210, USA.

The Journal of Biological Chemistry
|February 14, 2006
PubMed

Insights

Activating Transcription Factor 3 (ATF3) promotes apoptosis and cell cycle arrest. ATF3 deficiency protects against UV-induced cell death and Ras-mediated tumorigenesis, clarifying its regulatory roles.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • Activating Transcription Factor 3 (ATF3) is a stress-inducible transcription factor.
  • Existing literature presents conflicting roles for ATF3 in cell death and cell cycle regulation.
  • The precise functions of ATF3 in these cellular processes remain debated.

Purpose of the Study:

  • To elucidate the specific roles of ATF3 in cell death and cell cycle progression within mouse fibroblasts.
  • To resolve controversies regarding ATF3's function as a positive or negative regulator.
  • To investigate ATF3's impact on Ras-mediated transformation and tumorigenesis.

Main Methods:

  • Utilized ATF3-deficient (ATF3(-/-)) and wild-type (ATF3(+/+)) mouse fibroblasts.
  • Employed UV irradiation to induce apoptosis and a tet-off system for ATF3 ectopic expression.
  • Performed chromatin immunoprecipitation (ChIP) and transcription assays to assess gene regulation.
  • Analyzed cell cycle progression, Rb phosphorylation, and cyclin levels.
  • Assessed Ras transformation, soft agar colony formation, and xenograft tumor growth.

Main Results:

  • ATF3 deficiency conferred partial protection against UV-induced apoptosis.
  • Ectopic ATF3 expression induced apoptosis, while ATF3(-/-) cells showed more efficient G2 to S phase transition.
  • ATF3(-/-) fibroblasts exhibited enhanced Ras-mediated transformation, increased colony formation, and larger tumors.
  • ATF3 directly bound to the cyclin D1 promoter, repressing its transcription.

Conclusions:

  • ATF3 acts as a promoter of apoptosis and cell cycle arrest.
  • ATF3 suppresses Ras-mediated tumorigenesis, suggesting a tumor-suppressive role.
  • These findings clarify the dual roles of ATF3 in cell fate determination and cancer progression.

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