Cell cycle arrest induced by trichoplein depletion is independent of cilia assembly
Cell cycle arrest induced by trichoplein depletion is independent of cilia assembly
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Trichoplein 消耗诱导的细胞周期停滞与纤毛组装无关
DOI：
10.1002/jcp.30693
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发表时间：
2022-02-11
影响因子：
5.6
通讯作者：
Zhang, Xiujuan
中科院分区：
文献类型：
--
作者：
Huang, Min;Kong, Xinlong;Zhang, Xiujuan
纤毛组装和中心粒复制与细胞周期进程密切相关，纤毛分解的抑制阻碍了细胞周期进程。中心体蛋白三环素(Trichoplein)通过分解纤毛促进细胞周期进入G1-S期。在这项研究中，我们发现TCHP的缺失不仅阻止了细胞向S期的进展，而且还导致了细胞周期的退出和进入G0期。令人惊讶的是，我们发现TCHP诱导的G0滞留的丧失不能通过阻断纤毛的组装来逆转。在缺乏IFT20或CEP164的细胞中，编码纤毛发生关键因子的两个基因，TCHP的缺失仍导致G0停滞。在机制上，我们还发现TCHP耗竭诱导的细胞周期停滞不是通过中心体监视机制介导的，但需要抑制Rb或同时抑制Rb和P53信号通路来逆转细胞周期表型。总之，我们的研究为TCHP在细胞周期进程中的作用提供了新的见解。
Cilia assembly and centriole duplication are closely coordinated with cell cycle progression, and inhibition of cilia disassembly impedes cell cycle progression. The centrosomal protein trichoplein (TCHP) has been shown to promote cell cycle progression in the G1‐S phase by disassembling cilia. In this study, we showed that deletion of TCHP not only prevented the progression to the S phase but also resulted in cell cycle exit and entrance into G0 phase. Surprisingly, we found that loss of TCHP‐induced G0 arrest could not be reversed by blocking the assembly of cilia. In cells without IFT20 or CEP164, two genes encoding key factors for ciliogenesis, depletion of TCHP still led to G0 arrest. Mechanistically, we also found that TCHP depletion‐induced cell cycle arrest was not mediated through a centrosome surveillance mechanism, but inhibition of Rb or concomitant inhibition of both Rb and p53 signaling pathways was required to reverse the cell cycle phenotype. In conclusion, our study provides new insights into the function of TCHP in cell cycle progression.