IFT proteins interact with HSET to promote supernumerary centrosome clustering in mitosis

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  • Benjamin Vitre, Universite de Montpellier, Centrosome
  • ,
  • Nicolas Taulet, Universite de Montpellier, Centrosome
  • ,
  • Audrey Guesdon, Universite de Montpellier, Centrosome
  • ,
  • Audrey Douanier, Universite de Montpellier, Centrosome
  • ,
  • Aurelie Dosdane, Universite de Montpellier, Centrosome
  • ,
  • Melanie Cisneros, Universite de Montpellier, Centrosome
  • ,
  • Justine Maurin, Universite de Montpellier, Centrosome
  • ,
  • Sabrina Hettinger, Universite de Montpellier, Centrosome
  • ,
  • Christelle Anguille, Universite de Montpellier, Centrosome
  • ,
  • Michael Taschner, University of Lausanne
  • ,
  • Esben Lorentzen
  • Benedicte Delaval, Universite de Montpellier, Centrosome

Centrosome amplification is a hallmark of cancer, and centrosome clustering is essential for cancer cell survival. The mitotic kinesin HSET is an essential contributor to this process. Recent studies have highlighted novel functions for intraflagellar transport (IFT) proteins in regulating motors and mitotic processes. Here, using siRNA knock-down of various IFT proteins or AID-inducible degradation of endogenous IFT88 in combination with small-molecule inhibition of HSET, we show that IFT proteins together with HSET are required for efficient centrosome clustering. We identify a direct interaction between the kinesin HSET and IFT proteins, and we define how IFT proteins contribute to clustering dynamics during mitosis using high-resolution live imaging of centrosomes. Finally, we demonstrate the requirement of IFT88 for efficient centrosome clustering in a variety of cancer cell lines naturally harboring supernumerary centrosomes and its importance for cancer cell proliferation. Overall, our data unravel a novel role for the IFT machinery in centrosome clustering during mitosis in cells harboring supernumerary centrosomes.

OriginalsprogEngelsk
Artikelnummere49234
TidsskriftEMBO Reports
Vol/bind21
Nummer6
Antal sider15
ISSN1469-221X
DOI
StatusUdgivet - jun. 2020

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