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Cell cycle‐dependent ubiquitylation and destruction of NDE 1 by CDK 5‐ FBW 7 regulates ciliary length
Author(s) -
Maskey Dipak,
Marlin Matthew Caleb,
Kim Seokho,
Kim Sehyun,
Ong EChing,
Li Guangpu,
Tsiokas Leonidas
Publication year - 2015
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201490831
Subject(s) - ciliogenesis , microbiology and biotechnology , cyclin dependent kinase , biology , cell cycle , cilium , cell cycle protein , mitosis , cyclin dependent kinase 1 , cell , genetics
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 NDE 1 as a negative regulator of ciliary length and showed that its levels inversely correlate with ciliogenesis. Here, we identify the tumor suppressor FBW 7 (also known as FBXW 7, CDC 4, AGO , or SEL ‐10) as the E3 ligase that mediates the destruction of NDE 1 upon entry into G1. CDK 5, a kinase active in G1/G0, primes NDE 1 for FBW 7‐mediated recognition. Cells depleted of FBW 7 or CDK 5 show enhanced levels of NDE 1 and a reduction in ciliary length, which is corrected in cells depleted of both FBW 7 or CDK 5 and NDE 1. These data show that cell cycle‐dependent mechanisms can control ciliary length through a CDK 5‐ FBW 7‐ NDE 1 pathway.