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MBC in Press, published online ahead of print December 22, 2004
Mol. Biol. Cell 10.1091/mbc.E04-10-0939

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Submitted on October 28, 2004
Revised on December 10, 2004
Accepted on December 13, 2004

The FHA-domain Protein Cep170 Interacts with Plk1 and Serves as a Marker for Mature Centrioles

Giulia Guarguaglini,*{dagger}{ddagger} Peter I. Duncan,*{sect} York D. Stierhof,|| Tim Holmström,*¶ Stefan Duensing,# and Erich A. Nigg*

*Department of Cell Biology, Max-Planck Institute for Biochemistry, D-82152 Martinsried, Germany; ||Zentrum für Molekularbiologie der Pflanzen (ZMBP), Universität Tübingen, D-72076 Tübingen, Germany; #University of Pittsburgh Cancer Institute, Hillman Cancer Center, Pittsburgh, PA 15213

Monitoring Editor: Trisha Davis

We report the characterization of Cep170, a forkhead-associated (FHA) domain protein of previously unknown function. Cep170 was identified in a yeast two-hybrid screen for interactors of Polo-like kinase 1 (Plk1). In human cells, Cep170 is constantly expressed throughout the cell cycle but phosphorylated during mitosis. It interacts with Plk1 in vivo and can be phosphorylated by Plk1 in vitro, suggesting that it is a physiological substrate of this kinase. Both overexpression and siRNA-mediated depletion studies suggest a role for Cep170 in MT organization and cell morphology. Cep170 associates with centrosomes during interphase and with spindle microtubules during mitosis. As shown by immunoelectron-microscopy, Cep170 associates with subdistal appendages, typical of the mature mother centriole. Thus, anti-Cep170 antibodies stain only one centriole during G1, S and early G2, but two centrioles during late G2 phase of the cell cycle. We show that Cep170 labeling can be used to discriminate bonafide centriole overduplication from centriole amplification that results from aborted cell division.

Present addresses: {dagger}Institute of Molecular Biology and Pathology, CNR, c/o University of Rome "La Sapienza", 00185 Rome, Italy; {sect}Nutrition Department, Nestlé Research Center, CH-1000 Lausanne 26, Switzerland; Turku Centre for Biotechnology, FIN-20521Turku, Finland.

{ddagger}Corresponding author. E-mail: giulia.guarguaglini{at}uniromal.it




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