LUBAC regulates ciliogenesis by promoting CP110 removal from the mother centriole

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  • Xiao-Lin Shen
    Nanhu Laboratory, State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Beijing, China 1
  • Jin-Feng Yuan
    Nanhu Laboratory, State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Beijing, China 1
  • Xuan-He Qin
    School of Life Sciences and Technology, Tongji University, Shanghai, China 3
  • Guang-Ping Song
    Nanhu Laboratory, State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Beijing, China 1
  • Huai-Bin Hu
    Nanhu Laboratory, State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Beijing, China 1
  • Hai-Qing Tu
    Nanhu Laboratory, State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Beijing, China 1
  • Zeng-Qing Song
    Nanhu Laboratory, State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Beijing, China 1
  • Pei-Yao Li
    Nanhu Laboratory, State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Beijing, China 1
  • Yu-Ling Xu
    Nanhu Laboratory, State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Beijing, China 1
  • Sen Li
    Nanhu Laboratory, State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Beijing, China 1
  • Xiao-Xiao Jian
    Nanhu Laboratory, State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Beijing, China 1
  • Jia-Ning Li
    Nanhu Laboratory, State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Beijing, China 1
  • Chun-Yu He
    Nanhu Laboratory, State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Beijing, China 1
  • Xi-Ping Yu
    Nanhu Laboratory, State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Beijing, China 1
  • Li-Yun Liang
    Nanhu Laboratory, State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Beijing, China 1
  • Min Wu
    Nanhu Laboratory, State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Beijing, China 1
  • Qiu-Ying Han
    Nanhu Laboratory, State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Beijing, China 1
  • Kai Wang
    Nanhu Laboratory, State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Beijing, China 1
  • Ai-Ling Li
    Nanhu Laboratory, State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Beijing, China 1
  • Tao Zhou
    Nanhu Laboratory, State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Beijing, China 1
  • Yu-Cheng Zhang
    Nanhu Laboratory, State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Beijing, China 1
  • Na Wang
    Nanhu Laboratory, State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Beijing, China 1
  • Hui-Yan Li
    Nanhu Laboratory, State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Beijing, China 1

抄録

<jats:p>Primary cilia transduce diverse signals in embryonic development and adult tissues. Defective ciliogenesis results in a series of human disorders collectively known as ciliopathies. The CP110–CEP97 complex removal from the mother centriole is an early critical step for ciliogenesis, but the underlying mechanism for this step remains largely obscure. Here, we reveal that the linear ubiquitin chain assembly complex (LUBAC) plays an essential role in ciliogenesis by targeting the CP110–CEP97 complex. LUBAC specifically generates linear ubiquitin chains on CP110, which is required for CP110 removal from the mother centriole in ciliogenesis. We further identify that a pre-mRNA splicing factor, PRPF8, at the distal end of the mother centriole acts as the receptor of the linear ubiquitin chains to facilitate CP110 removal at the initial stage of ciliogenesis. Thus, our study reveals a direct mechanism of regulating CP110 removal in ciliogenesis and implicates the E3 ligase LUBAC as a potential therapy target of cilia-associated diseases, including ciliopathies and cancers.</jats:p>

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