期刊
PLOS BIOLOGY
卷 11, 期 8, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pbio.1001620
关键词
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资金
- National Basic Research Program of China (973 Program) [2010CB912101, 2012CB945001, 2011CB943902, 2010CB529901, 2011CB510104]
- Strategic Priority Research Program of the Chinese Academy of Sciences [XDA01010406, XDA01010405]
- National Natural Science Foundation of China [31171394, 31171414, 30623003, 81172449]
- National Key Basic Research and Development Program of China [2011CB915502]
- Welch Foundation [I-1603]
The evolutionarily conserved Hippo (Hpo) signaling pathway plays a pivotal role in organ size control by balancing cell proliferation and cell death. Here, we reported the identification of Par-1 as a regulator of the Hpo signaling pathway using a gain-of-function EP screen in Drosophila melanogaster. Overexpression of Par-1 elevated Yorkie activity, resulting in increased Hpo target gene expression and tissue overgrowth, while loss of Par-1 diminished Hpo target gene expression and reduced organ size. We demonstrated that par-1 functioned downstream of fat and expanded and upstream of hpo and salvador (sav). In addition, we also found that Par-1 physically interacted with Hpo and Sav and regulated the phosphorylation of Hpo at Ser30 to restrict its activity. Par-1 also inhibited the association of Hpo and Sav, resulting in Sav dephosphorylation and destabilization. Furthermore, we provided evidence that Par-1-induced Hpo regulation is conserved in mammalian cells. Taken together, our findings identified Par-1 as a novel component of the Hpo signaling network.
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