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2018/01/18
EGF receptor kinase suppresses ciliogenesis through activation of USP8 deubiquitinase

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Chemokines protect vascular smooth muscle cells from cell death induced by cyclic mechanical stretch.

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New photic stimulating system with white light-emitting diodes to elicit electroretinograms from zebrafish larvae.

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Potential protective function of the sterol regulatory element binding factor 1-fatty acid desaturase 12 axis in early-stage age-related macular degeneration

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Activation of Sterol Regulatory Element Binding Factors by Fenofibrate and Gemfibrozil Stimulates Myelination in Zebrafish

tEGF receptor kinase suppresses ciliogenesis through activation of USP8 deubiquitinase

                     
2018/01/18

Nature Communicationsvolume 9, Article number: 758 (2018)
doi:10.1038/s41467-018-03117-y

Kousuke Kasahara, Hiromasa Aoki, Tohru Kiyono, Shujie Wang, Harumi Kagiwada, Mizuki Yuge, Toshio Tanaka, Yuhei Nishimura, Akira Mizoguchi, Naoki Goshima & Masaki Inagaki

Abstract
Ciliogenesis is generally inhibited in dividing cells, however, it has been unclear which signaling cascades regulate the phenomenon. Here, we report that epidermal growth factor receptor (EGFR) kinase suppresses ciliogenesis by directly phosphorylating the deubiquitinase USP8 on Tyr-717 and Tyr-810 in RPE1 cells. These phosphorylations elevate the deubiquitinase activity, which then stabilizes the trichoplein-Aurora A pathway, an inhibitory mechanism of ciliogenesis. EGFR knockdown and serum starvation result in ciliogenesis through downregulation of the USP8-trichoplein-Aurora A signal. Moreover, primary cilia abrogation, which is induced upon IFT20 or Cep164 depletion, ameliorates the cell cycle arrest of EGFR knockdown cells. The present data reveal that the EGFR-USP8-trichoplein-Aurora A axis is a critical signaling cascade that restricts ciliogenesis in dividing cells, and functions to facilitate cell proliferation. We further show that usp8 knockout zebrafish develops ciliopathy-related phenotypes including cystic kidney, suggesting that USP8 is a regulator of ciliogenesis in vertebrates.

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Nature Communications

PubMed