Cep152 acts as a scaffold for recruitment of Plk4 and CPAP to the centrosome.
Both gain and loss of function studies have identified the Polo-like kinase Plk4/Sak as a crucial regulator of centriole biogenesis, but the mechanisms governing centrosome duplication are incompletely understood. In this study, we show that the pericentriolar material protein, Cep152, interacts with the distinctive cryptic Polo-box of Plk4 via its N-terminal domain and is required for Plk4-induced centriole overduplication. Reduction of endogenous Cep152 levels results in a failure in centriole duplication, loss of centrioles, and formation of monopolar mitotic spindles. Interfering with Cep152 function prevents recruitment of Plk4 to the centrosome and promotes loss of CPAP, a protein required for the control of centriole length in Plk4-regulated centriole biogenesis. Our results suggest that Cep152 recruits Plk4 and CPAP to the centrosome to ensure a faithful centrosome duplication process.
Cell Cycle Control and Carcinogenesis, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
Onur
O
Cizmecioglu
Marc
M
Arnold
Ramona
R
Bahtz
Florian
F
Settele
Lena
L
Ehret
Uta
U
Haselmann-Weiss
Claude
C
Antony
Ingrid
I
Hoffmann
D000818:Animals; D002453:Cell Cycle / Q000502:physiology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D018385:Centrosome / Q000378:metabolism*; D036681:Fluorescence Recovery After Photobleaching; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D008941:Spindle Apparatus / Q000378:metabolism
C414735:CENPJ protein, human; C551028:CEP152 protein, human; D018797:Cell Cycle Proteins; D008869:Microtubule-Associated Proteins; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; C490219:PLK4 protein, human; D017346:Protein Serine-Threonine Kinases