Polo-like kinase 4 autodestructs by generating its slimb-binding phosphodegron

Joseph E. Klebba, Daniel W. Buster, Annie L. Nguyen, Stephen Swatkoski, Marjan Gucek, Nasser M. Rusan, Gregory C. Rogers

Research output: Contribution to journalArticlepeer-review

57 Scopus citations


Polo-like kinase 4 (Plk4) is a conserved master regulator of centriole assembly [1]. Previously, we found that Drosophila Plk4 protein levels are actively suppressed during interphase [2]. Degradation of interphase Plk4 prevents centriole overduplication and is mediated by the ubiquitin-ligase complex SCFSlimb/βTrCP [3, 4]. Since Plk4 stability depends on its activity [5, 6], we studied the consequences of inactivating Plk4 or perturbing its phosphorylation state within its Slimb-recognition motif (SRM). Mass spectrometry of in-vitro-phosphorylated Plk4 and Plk4 purified from cells reveals that it is directly responsible for extensively autophosphorylating and generating its Slimb-binding phosphodegron. Phosphorylatable residues within this regulatory region were systematically mutated to determine their impact on Plk4 protein levels and centriole duplication when expressed in S2 cells. Notably, autophosphorylation of a single residue (Ser293) within the SRM is critical for Slimb binding and ubiquitination. Our data also demonstrate that autophosphorylation of numerous residues flanking S293 collectively contribute to establishing a high-affinity binding site for SCFSlimb. Taken together, our findings suggest that Plk4 directly generates its own phosphodegron and can do so without the assistance of an additional kinase(s).

Original languageEnglish (US)
Pages (from-to)2255-2261
Number of pages7
JournalCurrent Biology
Issue number22
StatePublished - Nov 18 2013

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology
  • General Agricultural and Biological Sciences


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