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Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
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Adenovirus E1A targets p400 to induce the cellular oncoprotein Myc

Kathryn A Tworkowski1, Abhishek A Chakraborty, Andrew V Samuelson

  • 1Cold Spring Harbor Laboratory, and Howard Hughes Medical Institute, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.

Proceedings of the National Academy of Sciences of the United States of America
|April 17, 2008
PubMed

Insights

Adenovirus E1A protein stabilizes the Myc oncoprotein through p400, driving oncogenesis. This interaction is crucial for E1A

Area of Science:

  • Molecular Biology
  • Oncology
  • Virology

Background:

  • Adenovirus E1A protein is a key driver of oncogenesis, regulating cellular growth pathways.
  • The interaction between E1A and p400 is vital for E1A's functions, but its downstream target remained unidentified.

Purpose of the Study:

  • To identify the downstream target of the Adenovirus E1A-p400 interaction.
  • To elucidate the role of Myc in E1A-mediated oncogenesis.

Main Methods:

  • Investigated the interaction between E1A, p400, and Myc.
  • Assessed the impact of E1A on Myc protein stability and localization.
  • Analyzed Myc-dependent gene expression and apoptosis induction.
  • Utilized mutant E1A and Myc expression systems.

Main Results:

  • Demonstrated that Adenovirus E1A stabilizes Myc protein through p400.
  • Showed E1A promotes Myc and p400 coassociation at Myc target genes, enhancing transcription.
  • Confirmed E1A requires Myc for activating Myc-dependent gene expression and inducing apoptosis.
  • Found forced Myc expression rescues the activity of E1A mutants lacking p400 binding.

Conclusions:

  • Myc, acting through p400, is an essential downstream target of Adenovirus E1A.
  • This E1A-Myc-p400 axis is critical for E1A's oncogenic activities, including gene regulation and apoptosis induction.

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