title: Cell cycle-dependent ubiquitylation and destruction of NDE1 by CDK5-FBW7 regulates ciliary length.
abstract: Primary cilia start forming within the G1 phase of the cell cycle and continue to grow as cells exit the cell cycle (G0). They start resorbing when cells re-enter the cell cycle (S phase) and are practically invisible in mitosis. The mechanisms by which cilium biogenesis and disassembly are coupled to the cell cycle are complex and not well understood. We previously identified the centrosomal phosphoprotein NDE1 as a negative regulator of ciliary length and showed that its levels inversely correlate with ciliogenesis. Here, we identify the tumor suppressor FBW7 (also known as FBXW7, CDC4, AGO, or SEL-10) as the E3 ligase that mediates the destruction of NDE1 upon entry into G1. CDK5, a kinase active in G1/G0, primes NDE1 for FBW7-mediated recognition. Cells depleted of FBW7 or CDK5 show enhanced levels of NDE1 and a reduction in ciliary length, which is corrected in cells depleted of both FBW7 or CDK5 and NDE1. These data show that cell cycle-dependent mechanisms can control ciliary length through a CDK5-FBW7-NDE1 pathway.
authors.affiliation: Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Dipak
authors.initials: D
authors.lastname: Maskey
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Matthew Caleb
authors.initials: MC
authors.lastname: Marlin
authors.affiliation: Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Seokho
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Sehyun
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: E-Ching
authors.initials: EC
authors.lastname: Ong
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Guangpu
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA ltsiokas@ouhsc.edu.
authors.forename: Leonidas
authors.initials: L
authors.lastname: Tsiokas
mesh_terms: D000818:Animals; D041702:BALB 3T3 Cells; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002923:Cilia / Q000235:genetics / Q000378:metabolism; D051360:Cyclin-Dependent Kinase 5 / Q000235:genetics / Q000378:metabolism*; D044783:F-Box Proteins / Q000235:genetics / Q000378:metabolism*; D000073979:F-Box-WD Repeat-Containing Protein 7; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D059748:Proteolysis; D015398:Signal Transduction / Q000502:physiology; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination / Q000502:physiology*
chemical_list: D018797:Cell Cycle Proteins; D044783:F-Box Proteins; D000073979:F-Box-WD Repeat-Containing Protein 7; C513273:FBXW7 protein, human; C513272:Fbxw7 protein, mouse; D008869:Microtubule-Associated Proteins; C525094:Nde1 protein, human; C531336:Nde1 protein, mouse; D044767:Ubiquitin-Protein Ligases; D051360:Cyclin-Dependent Kinase 5; C495905:CDK5 protein, human; C495906:Cdk5 protein, mouse
keywords: CDK5; FBW7; NDE1; cilia; p35