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Autoinhibition and relief mechanism for Polo-like kinase 4

Joseph E Klebba1, Daniel W Buster1, Tiffany A McLamarrah1

  • 1Department of Cellular and Molecular Medicine, University of Arizona Cancer Center, University of Arizona, Tucson, AZ 85724; and.

Proceedings of the National Academy of Sciences of the United States of America
|February 4, 2015
PubMed

Insights

Polo-like kinase 4 (Plk4) regulation involves a complex autoinhibitory mechanism. This process, involving dimerization and phosphorylation, controls centriole duplication and prevents amplification.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Polo-like kinase 4 (Plk4) is crucial for centriole duplication.
  • Plk4 hyperactivity leads to centriole amplification.
  • The role of Plk4's third Polo box (PB3) domain was previously unclear.

Purpose of the Study:

  • To functionally analyze the structural domains of Plk4.
  • To elucidate the regulatory and activation mechanisms of Plk4.
  • To understand how Plk4 controls centriole duplication.

Main Methods:

  • Functional analysis of Plk4 structural domains.
  • Investigation of autoinhibition and autophosphorylation mechanisms.
  • Study of Plk4 homodimerization and its regulation.

Main Results:

  • Plk4 exhibits a conserved autoinhibitory mechanism mediated by the L1 linker.
  • Autoinhibition is relieved by homodimerization, PB3, and L1 autophosphorylation.
  • Autophosphorylation of the second linker promotes Plk4 homodimer dissociation.

Conclusions:

  • Autoinhibition delays Plk4 activation until dimerization occurs.
  • A complex regulatory mechanism governs Plk4 activation and centriole duplication.
  • PB3 and specific phosphorylation sites play key roles in Plk4 regulation.
Keywords:
Polo boxPolo-like kinase 4autoinhibitioncentriolecentrosome

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