期刊
JOURNAL OF CELL SCIENCE
卷 132, 期 2, 页码 -出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.220384
关键词
Gli1; Hedgehog signaling; Plk1 kinase; Cell cycle; Phosphorylation
类别
资金
- Ministry of Science and Technology of the People's Republic of China [2016YFA0100501, 2016YFA0500201]
- National Natural Science Foundation of China (NSFC) [31520103906, 31430051, 31571386, 91854204]
Hedgehog (Hh) signaling is a highly conserved cell signaling pathway important for cell life, development and tumorigenesis. Increasing evidence suggests that the Hh signaling pathway functions in certain phases of the cell cycle. However, the coordination between Hh signaling and cell cycle control remains poorly understood. Here, we show that polo-like kinase-1 (Plk1), a critical protein kinase regulating many processes during the cell cycle, also regulates Hh signaling by phosphorylating and inhibiting Gli1, a downstream transcription factor of the Hh signaling pathway. Gli1 expression increases along with Hh signaling activation, leading to upregulation of Hh target genes, including cyclin E, during the G1 and S phases. Gli1 is phosphorylated at S481 by Plk1, and this phosphorylation facilitates the nuclear export and binding of Gli1 with its negative regulator Sufu, leading to a reduction in Hh signaling activity. Inhibition of Plk1 kinase activity led to Gli1 maintaining is role in promoting downstream gene expression. Collectively, our data reveal a novel mechanism regarding the crosstalk between Hh signaling and cell cycle control.
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