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

Benjamin Vitre; Nicolas Taulet; Audrey Guesdon; Audrey Douanier; Aurelie Dosdane; Melanie Cisneros; Justine Maurin; Sabrina Hettinger; Christelle Anguille; Michael Taschner; Esben Lorentzen; Benedicte Delaval

doi:10.15252/embr.201949234

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

Benjamin Vitre^*, Nicolas Taulet, Audrey Guesdon, Audrey Douanier, Aurelie Dosdane, Melanie Cisneros, Justine Maurin, Sabrina Hettinger, Christelle Anguille, Michael Taschner, Esben Lorentzen, Benedicte Delaval

^*Corresponding author for this work

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Abstract

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.

Original language	English
Article number	e49234
Journal	EMBO Reports
Volume	21
Issue	6
Number of pages	15
ISSN	1469-221X
DOIs	https://doi.org/10.15252/embr.201949234
Publication status	Published - Jun 2020

Keywords

cancer
centrosome clustering
HSET/KifC1
IFT proteins
mitosis

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10.15252/embr.201949234Licence: CC BY

embr.201949234Final published version, 1.83 MBLicence: CC BY

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title = "IFT proteins interact with HSET to promote supernumerary centrosome clustering in mitosis",

abstract = "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.",

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author = "Benjamin Vitre and Nicolas Taulet and Audrey Guesdon and Audrey Douanier and Aurelie Dosdane and Melanie Cisneros and Justine Maurin and Sabrina Hettinger and Christelle Anguille and Michael Taschner and Esben Lorentzen and Benedicte Delaval",

year = "2020",

month = jun,

doi = "10.15252/embr.201949234",

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AU - Vitre, Benjamin

AU - Taulet, Nicolas

AU - Guesdon, Audrey

AU - Douanier, Audrey

AU - Dosdane, Aurelie

AU - Cisneros, Melanie

AU - Maurin, Justine

AU - Hettinger, Sabrina

AU - Anguille, Christelle

AU - Taschner, Michael

AU - Lorentzen, Esben

AU - Delaval, Benedicte

PY - 2020/6

Y1 - 2020/6

N2 - 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.

AB - 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.

KW - cancer

KW - centrosome clustering

KW - HSET/KifC1

KW - IFT proteins

KW - mitosis

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

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