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

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 an...

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Vydáno v:EMBO reports Ročník 21; číslo 6; s. e49234 - n/a
Hlavní autoři: Vitre, Benjamin, Taulet, Nicolas, Guesdon, Audrey, Douanier, Audrey, Dosdane, Aurelie, Cisneros, Melanie, Maurin, Justine, Hettinger, Sabrina, Anguille, Christelle, Taschner, Michael, Lorentzen, Esben, Delaval, Benedicte
Médium: Journal Article
Jazyk:angličtina
Vydáno: London Nature Publishing Group UK 04.06.2020
Springer Nature B.V
EMBO Press
John Wiley and Sons Inc
Témata:
Amplification
Cancer
Carrier Proteins - genetics
Cell proliferation
Cell survival
Centrosome - metabolism
centrosome clustering
Centrosomes
Cluster Analysis
Clustering
Depletion
EMBO05
EMBO06
HSET/KifC1
IFT proteins
Kinesin
Kinesin - genetics
Kinesin - metabolism
Life Sciences
Microtubules
Mitosis
Mitosis - genetics
Protein transport
Proteins
siRNA
Spindles
Supernumerary
Survival
Tumor cell lines
cancer
HSET/KifC1
mitosis
centrosome clustering
IFT proteins
Cell Cycle
mitosis Subject Categories Cell Adhesion
Polarity & Cytoskeleton
ISSN:1469-221X, 1469-3178, 1469-3178
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Shrnutí: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. Synopsis Cancer cells with centrosome amplification cluster their centrosomes to form bipolar mitotic spindles. This study reveals that intraflagellar transport (IFT) proteins are required for centrosome clustering in mitosis by interacting with the kinesin HSET. Depleting IFT52 or IFT88 interferes with centrosome clustering. IFT complex mediates centrosome clustering by directly interacting with the kinesin HSET. IFT88 depletion reduces HSET turnover on mitotic spindle microtubules. IFT52 depletion reduces centrosome clustering dynamics in late G2 and mitosis. Depletion of IFT88 in cancer cells exhibiting centrosome amplification leads to reduced proliferation and survival. Graphical Abstract Cancer cells with centrosome amplification cluster their centrosomes to form bipolar mitotic spindles. This study reveals that intraflagellar transport (IFT) proteins are required for centrosome clustering in mitosis by interacting with the kinesin HSET.
Bibliografie:ObjectType-Article-1
SourceType-Scholarly Journals-1
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ISSN:1469-221X
1469-3178
1469-3178
DOI:10.15252/embr.201949234