期刊
JOURNAL OF CELL SCIENCE
卷 125, 期 5, 页码 1342-1352出版社
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/jcs.099887
关键词
APC/C; Centrosome; Centriole duplication; Centriole number; Daughter centriole; STIL
类别
资金
- Swiss National Science Foundation [31003A_132428/1]
- Werner Siemens Foundation (Zug, Switzerland)
- Boehringer-Ingelheim Fonds
- International Max Planck Research School for Molecular and Cellular Life Sciences (Martinsried, Germany)
- Swiss National Science Foundation (SNF) [31003A_132428] Funding Source: Swiss National Science Foundation (SNF)
Control of centriole number is crucial for genome stability and ciliogenesis. Here, we characterize the role of human STIL, a protein that displays distant sequence similarity to the centriole duplication factors Ana2 in Drosophila and SAS-5 in Caenorhabditis elegans. Using RNA interference, we show that STIL is required for centriole duplication in human cells. Conversely, overexpression of STIL triggers the near-simultaneous formation of multiple daughter centrioles surrounding each mother, which is highly reminiscent of the phenotype produced by overexpression of the polo-like kinase PLK4 or the spindle assembly abnormal protein 6 homolog (SAS-6). We further show, by fluorescence and immunoelectron microscopy, that STIL is recruited to nascent daughter centrioles at the onset of centriole duplication and degraded, in an APC/CCdc20-Cdh1-dependent manner, upon passage through mitosis. We did not detect a stable complex between STIL and SAS-6, but the two proteins resemble each other with regard to both localization and cell cycle control of expression. Thus, STIL cooperates with SAS-6 and PLK4 in the control of centriole number and represents a key centriole duplication factor in human cells.
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