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Publication List English
2024/08/06
2024/05/21
2021/10/31
Generation of a Transgenic Zebrafish Line for In Vivo Assessment of Hepatic Apoptosis
2021/08/19
2021/07/09
Establishment of a Quality Control Protocol for Zebrafish Developmental Toxicity Studies
2020/10/13
2020/05/28
A novel orexin antagonist from a natural plant was discovered using zebrafish behavioural analysis
2019/10/15
C3orf70 Is Involved in Neural and Neurobehavioral Development
2019/09/22
2019/07/17
Aging-associated microstructural deterioration of vertebra in zebrafish
EGF 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.
