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Dynamic interplay between nitration and phosphorylation of tubulin cofactor B in the control of microtubule dynamics

Suresh K Rayala1, Emil Martin, Iraida G Sharina

  • 1Department of Molecular and Cellular Oncology, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.

Proceedings of the National Academy of Sciences of the United States of America
|December 1, 2007
PubMed

Insights

Tubulin cofactor B (TCoB) is nitrated, attenuating microtubule synthesis. This nitration antagonizes TCoB phosphorylation, revealing a feedback loop regulating microtubule dynamics.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Tubulin cofactor B (TCoB) is crucial for microtubule dynamics and alpha-beta tubulin dimerization.
  • p21-activated kinase 1 (Pak1) phosphorylates TCoB, essential for microtubule regrowth.
  • No upstream regulators antagonizing TCoB function were previously identified.

Purpose of the Study:

  • To identify upstream signaling molecules that antagonize TCoB function.
  • To investigate the role of TCoB nitration in microtubule regulation.
  • To elucidate the interplay between TCoB nitration and phosphorylation.

Main Methods:

  • Protein analysis to identify TCoB nitration sites.
  • Biochemical assays to assess the impact of nitration on TCoB function.
  • Cellular experiments to study microtubule dynamics and signaling pathways.

Main Results:

  • TCoB is significantly nitrated on Tyr-64 and Tyr-98.
  • Nitrated TCoB attenuates the synthesis of new microtubules.
  • TCoB nitration antagonizes Pak1-dependent phosphorylation, with optimal nitration requiring Pak1 phosphorylation sites.
  • TCoB is the third identified cytoskeleton protein to undergo nitration.

Conclusions:

  • TCoB nitration represents a novel mechanism for regulating microtubule dynamics.
  • Nitric oxide signaling is integrated with growth factor signaling to control microtubule equilibrium.
  • A feedback mechanism involving TCoB nitration and phosphorylation is proposed to regulate microtubule regrowth.

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