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Multimerization of polyomavirus middle-T antigen

M Senften¹, S Dilworth, K Ballmer-Hofer

¹Friedrich Miescher Institute, Basel, Switzerland.

Journal of Virology

|September 1, 1997

Summary

Polyomavirus middle-T antigen forms dimers for cell signaling, requiring membrane association but not 14-3-3 proteins for oncogenic activity. Membrane targeting is key for middle-T antigen dimerization and oncogenesis.

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Area of Science:

Molecular Biology
Cell Biology
Virology

Background:

The polyomavirus middle-T antigen is an oncogenic protein that interacts with cellular proteins involved in mitogenic signaling.
It mimics cellular tyrosine kinase growth factor receptors, initiating signaling cascades upon ligand binding and receptor dimerization.
Receptor phosphorylation and subsequent recruitment of signaling molecules are crucial downstream events.

Purpose of the Study:

To investigate whether polyomavirus middle-T antigen forms dimeric signaling complexes, similar to tyrosine kinase growth factor receptors.
To determine the roles of membrane association and 14-3-3 protein binding in middle-T antigen dimerization and oncogenic function.

Main Methods:

Utilized chimeric middle-T antigen constructs with altered membrane-targeting sequences.
Investigated middle-T antigen mutants deficient in 14-3-3 protein association.
Assessed dimerization and oncogenic potential of modified middle-T antigen variants.

Main Results:

Membrane association is a prerequisite for middle-T antigen multimerization, likely dimer formation.
A chimeric middle-T antigen with a viral membrane-targeting sequence retained the ability to dimerize.
Mutants lacking 14-3-3 protein binding (d18, S257A) failed to dimerize but remained oncogenic.

Conclusions:

Membrane association and 14-3-3 protein binding are both necessary for middle-T antigen dimer formation.
Membrane association alone is sufficient for the oncogenic activity of middle-T antigen, independent of dimerization or 14-3-3 binding.

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