Autoinhibition and relief mechanism for polo-like kinase 4

Joseph E. Klebba, Daniel W. Buster, Tiffany A. McLamarrah, Nasser M. Rusan, Gregory C. Rogers

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Polo-like kinase 4 (Plk4) is a master regulator of centriole duplication, and its hyperactivity induces centriole amplification. Homodimeric Plk4 has been shown to be ubiquitinated as a result of autophosphorylation, thus promoting its own degradation and preventing centriole amplification. Unlike other Plks, Plk4 contains three rather than two Polo box domains, and the function of its third Polo box (PB3) is unclear. Here, we performed a functional analysis of Plk4's structural domains. Like other Plks, Plk4 possesses a previously unidentified autoinhibitory mechanism mediated by a linker (L1) near the kinase domain. Thus, autoinhibition is a conserved feature of Plks. In the case of Plk4, autoinhibition is relieved after homodimerization and is accomplished by PB3 and by autophosphorylation of L1. In contrast, autophosphorylation of the second linker promotes separation of the Plk4 homodimer. Therefore, autoinhibition delays the multiple consequences of activation until Plk4 dimerizes. These findings reveal a complex mechanism of Plk4 regulation and activation which govern the process of centriole duplication.

Original languageEnglish (US)
Pages (from-to)E657-E666
JournalProceedings of the National Academy of Sciences of the United States of America
Volume112
Issue number7
DOIs
StatePublished - Feb 17 2015

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Phosphotransferases
Centrioles

Keywords

  • Autoinhibition
  • Centriole
  • Centrosome
  • Polo box
  • Polo-like kinase 4

ASJC Scopus subject areas

  • General

Cite this

Autoinhibition and relief mechanism for polo-like kinase 4. / Klebba, Joseph E.; Buster, Daniel W.; McLamarrah, Tiffany A.; Rusan, Nasser M.; Rogers, Gregory C.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 112, No. 7, 17.02.2015, p. E657-E666.

Research output: Contribution to journalArticle

Klebba, Joseph E. ; Buster, Daniel W. ; McLamarrah, Tiffany A. ; Rusan, Nasser M. ; Rogers, Gregory C. / Autoinhibition and relief mechanism for polo-like kinase 4. In: Proceedings of the National Academy of Sciences of the United States of America. 2015 ; Vol. 112, No. 7. pp. E657-E666.
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