期刊
EMBO REPORTS
卷 22, 期 2, 页码 -出版社
WILEY
DOI: 10.15252/embr.202051127
关键词
centrosomes; SAS‐ 4; p53; USP28; 53BP1
资金
- Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) [BA 5810/1-1]
- Projekt DEAL
The formation and function of centrosomes are crucial for mouse development, as centriole loss can lead to cell cycle arrest and cell death. The peripheral proteins 53BP1 and USP28 are upstream of p53 in the absence of centrioles, participating in the regulation of cell mitosis.
Centrosomes, composed of two centrioles and pericentriolar material, organize mitotic spindles during cell division and template cilia during interphase. The first few divisions during mouse development occur without centrioles, which form around embryonic day (E) 3. However, disruption of centriole biogenesis in Sas-4 null mice leads to embryonic arrest around E9. Centriole loss in Sas-4(-/-) embryos causes prolonged mitosis and p53-dependent cell death. Studies in vitro discovered a similar USP28-, 53BP1-, and p53-dependent mitotic surveillance pathway that leads to cell cycle arrest. In this study, we show that an analogous pathway is conserved in vivo where 53BP1 and USP28 are upstream of p53 in Sas-4(-/-) embryos. The data indicate that the pathway is established around E7 of development, four days after the centrioles appear. Our data suggest that the newly formed centrioles gradually mature to participate in mitosis and cilia formation around the beginning of gastrulation, coinciding with the activation of mitotic surveillance pathway upon centriole loss.
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