Genome-wide screen identifies novel machineries required for both ciliogenesis and cell cycle arrest upon serum starvation

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Biogenesis of the primary cilium, a cellular organelle mediating various signaling pathways, is generally coordinated with cell cycle exit/re-entry. Although the dynamic cell cycle-associated profile of the primary cilium has been largely accepted, the mechanism governing the link between ciliogenesis and cell cycle progression has been poorly understood. Using a human genome-wide RNAi screen, we identify genes encoding subunits of the spliceosome and proteasome as novel regulators of ciliogenesis. We demonstrate that 1) the mRNA processing-related hits are essential for RNA expression of molecules acting in cilia disassembly, such as AURKA and PLK1, and 2) the ubiquitin-proteasome systems (UPS)-involved hits are necessary for proteolysis of molecules acting in cilia assembly, such as IFT88 and CPAP. In particular, we show that these screen hit-associated mechanisms are crucial for both cilia assembly and cell cycle arrest in response to serum withdrawal. Finally, our data suggest that the mRNA processing mechanism may modulate the UPS-dependent decay of cilia assembly regulators to control ciliary resorption-coupled cell cycle re-entry. (C) 2016 The Authors. Published by Elsevier B.V
Publisher
ELSEVIER SCIENCE BV
Issue Date
2016-06
Language
English
Article Type
Article
Keywords

PRIMARY CILIUM; CILIARY LOCALIZATION; PROLIFERATING CELLS; ACTIVATION; PROGRESSION; TRANSITION; PROTEIN; TRAFFICKING; STABILITY; REENTRY

Citation

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, v.1863, no.6, pp.1307 - 1318

ISSN
0167-4889
DOI
10.1016/j.bbamcr.2016.03.021
URI
http://hdl.handle.net/10203/209472
Appears in Collection
MSE-Journal Papers(저널논문)
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