title: Plk2 regulates centriole duplication through phosphorylation-mediated degradation of Fbxw7 (human Cdc4).
abstract: Polo-like kinases (Plks) perform crucial functions during mitosis, cytokinesis and centriole duplication. Plk2 is activated in early G1 phase and is involved in the reproduction of centrosomes. However, the mechanisms underlying Plk2-induced centriole duplication are incompletely understood. Here, we show that Plk2 directly targets the F-box protein F-box/WD repeat-containing protein 7 (Fbxw7), which is a regulator of the ubiquitin-mediated degradation of cyclin E. Plk2 phosphorylates Fbxw7 on serine 176 and the two proteins form a complex in vitro and in vivo. Phosphorylation of Fbxw7 by Plk2 induces destabilization of the F-box protein resulting in accumulation of cyclin E and increased potential for centriole reproduction. In addition, loss of Fbxw7 in human cells leads to uncontrolled centriole duplication, highlighting the importance of Fbxw7 regulation by Plk2. These findings define a previously unknown Plk2-dependent pathway involved at the onset of S phase and in centrosome duplication.
authors.affiliation: Cell cycle Control and Carcinogenesis (F045), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 242, 69120 Heidelberg,  Germany.
authors.forename: Onur
authors.initials: O
authors.lastname: Cizmecioglu
authors.forename: Annekatrin
authors.initials: A
authors.lastname: Krause
authors.forename: Ramona
authors.initials: R
authors.lastname: Bahtz
authors.forename: Lena
authors.initials: L
authors.lastname: Ehret
authors.forename: Nisar
authors.initials: N
authors.lastname: Malek
authors.forename: Ingrid
authors.initials: I
authors.lastname: Hoffmann
mesh_terms: D018797:Cell Cycle Proteins / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D002502:Centrioles / Q000378:metabolism*; D019927:Cyclin E / Q000378:metabolism; D044783:F-Box Proteins / Q000737:chemistry / Q000378:metabolism*; D000073979:F-Box-WD Repeat-Containing Protein 7; D006801:Humans; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D011485:Protein Binding; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D055550:Protein Stability; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D018797:Cell Cycle Proteins; D019927:Cyclin E; D044783:F-Box Proteins; D000073979:F-Box-WD Repeat-Containing Protein 7; C513273:FBXW7 protein, human; D010768:Phosphoserine; D044767:Ubiquitin-Protein Ligases; D011494:Protein Kinases; C496126:PLK2 protein, human; D017346:Protein Serine-Threonine Kinases