Article (Scientific journals)
INPP5E Preserves Genomic Stability through Regulation of Mitosis
Sierra Potchanant, EA; Cerabona, D; Sater, ZA et al.
2017In Molecular and Cellular Biology, 37 (6), p. 500-516
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Keywords :
inositide; phosphoinositide; primary cilium; Inpp5e; phosphatase; 5-phosphatase
Abstract :
[en] The partially understood phosphoinositide signaling cascade regulates multiple aspects of cellular metabolism. Previous studies revealed that INPP5E, the inositol polyphosphate-5-phosphatase that is mutated in the developmental disorders Joubert and MORM syndromes, is essential for the function of the primary cilium and maintenance of phosphoinositide balance in nondividing cells. Here, we report that INPP5E further contributes to cellular homeostasis by regulating cell division. We found that silencing or genetic knockout of INPP5E in human and murine cells impairs the spindle assembly checkpoint, centrosome and spindle function, and maintenance of chromosomal integrity. Consistent with a cell cycle regulatory role, we found that INPP5E expression is cell cycle dependent, peaking at mitotic entry. INPP5E localizes to centrosomes, chromosomes, and kinetochores in early mitosis and shuttles to the midzone spindle at mitotic exit. Our findings identify the previously unknown, essential role of INPP5E in mitosis and prevention of aneuploidy, providing a new perspective on the function of this phosphoinositide phosphatase in health and development.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Sierra Potchanant, EA
Cerabona, D
Sater, ZA
He, Y
Sun, Z
Gehlhausen, J
Schurmans, Stéphane  ;  Université de Liège - ULiège > Département des sciences fonctionnelles (DSF) > Biochimie métabolique vétérinaire
Gayral, S
Nalepa, G
Language :
English
Title :
INPP5E Preserves Genomic Stability through Regulation of Mitosis
Publication date :
2017
Journal title :
Molecular and Cellular Biology
ISSN :
0270-7306
eISSN :
1098-5549
Publisher :
American Society for Microbiology, Washington, United States - District of Columbia
Volume :
37
Issue :
6
Pages :
500-516
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 28 September 2017

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