Functional and Structural Mimicry of Cellular Protein Kinase A Anchoring Proteins by a Viral Oncoprotein

Cason R King1, Michael J Cohen1, Gregory J Fonseca1

  • 1Department of Microbiology & Immunology, University of Western Ontario, London, Ontario, Canada.

Plos Pathogens
|May 4, 2016
PubMed

Insights

Adenovirus E1A protein acts as a viral A-kinase anchoring protein (AKAP), mimicking cellular AKAPs to hijack protein kinase A (PKA) signaling. This viral AKAP activity is crucial for efficient viral gene expression and replication.

Area of Science:

  • Virology
  • Molecular Biology
  • Cellular Signaling

Background:

  • Small DNA tumor viruses utilize oncoproteins to manipulate host cell processes.
  • Adenovirus E1A protein is known to deregulate cAMP signaling for viral gene activation.

Purpose of the Study:

  • To investigate the mechanism by which adenovirus E1A protein interacts with and deregulates cellular signaling pathways.
  • To determine if E1A mimics cellular regulators to control host cell machinery.

Main Methods:

  • Structural and functional analysis of adenovirus E1A protein.
  • Investigating interactions between E1A and protein kinase A (PKA) regulatory subunits.
  • Assessing the role of E1A in competing with cellular A-kinase anchoring proteins (AKAPs).

Main Results:

  • Adenovirus E1A protein structurally and functionally mimics cellular AKAPs.
  • E1A interacts with PKA regulatory subunits, relocating PKA to the nucleus.
  • E1A competes with endogenous AKAPs for PKA binding, promoting viral transcription and replication.

Conclusions:

  • Adenovirus E1A functions as the first identified viral AKAP.
  • E1A's mimicry of AKAP domains represents a novel strategy for viral subversion of cellular signaling pathways.
  • This mechanism is critical for efficient viral gene expression and progeny production.

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