Huang, H.L., Wang, S., Yin, M.X., Dong, L., Wang, C., Wu, W., Lu, Y., Feng, M., Dai, C., Guo, X., Li, L., Zhao, B., Zhou, Z., Ji, H., Jiang, J., Zhao, Y., Liu, X.Y., Zhang, L. (2013). Par-1 regulates tissue growth by influencing hippo phosphorylation status and hippo-salvador association.  PLoS Biol. 11(8): e1001620.

FBrf0222342

Research paper

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.

PMC3735459 (PMC) (EuropePMC)