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General Comment |
NOS1AP functionally associates with YAP to regulate Hippo signaling. Clattenburg L et al. (2015) Deregulation of cellular polarity proteins and their associated complexes lead to changes in cell migration and proliferation. The nitric oxide synthase 1 adaptor protein (NOS1AP) associates with the tumor suppressor protein scribble to control cell migration and oncogenic transformation. However, how NOS1AP is linked to the cell signaling events that curbs oncogenic progression has remained elusive. Here we identify several novel NOS1AP isoforms, NOS1APd, NOS1APe, and NOS1APf, with distinct cellular localization. We show that isoforms with a membrane-interacting PTB domain can associate with scribble and recognizes acidic phospholipids. In a screen to identify novel binding proteins, we have discovered a complex consisting of NOS1AP and the transcriptional co-activator YAP linking NOS1AP to the Hippo signaling pathway. Silencing NOS1AP reduces the phosphorylation of YAP and of the upstream kinase Lats1. Conversely, expression of NOS1AP promotes YAP and Lats1 phosphorylation, which correlates with reduced TEAD activity and restricted cell proliferation. Together these data implicate a role for NOS1AP in regulation of core Hippo signaling and are consistent with the idea that NOS1AP functions as a tumor suppressor.//////////////////
NCBI Summary:
This gene encodes a cytosolic protein that binds to the signaling molecule, neuronal nitric oxide synthase (nNOS). This protein has a C-terminal PDZ-binding domain that mediates interactions with nNOS and an N-terminal phosphotyrosine binding (PTB) domain that binds to the small monomeric G protein, Dexras1. Studies of the related mouse and rat proteins have shown that this protein functions as an adapter protein linking nNOS to specific targets, such as Dexras1 and the synapsins. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Sep 2009]
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