Par-1 Regulates Tissue Growth by Influencing Hippo Phosphorylation Status and Hippo-Salvador Association

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. © 2013 huang et al.