The Hippo Signaling Network and Its Biological Functions

Abstract

<p class="first" id="P1">Hippo signaling is an evolutionarily conserved network that plays a central role in regulating cell proliferation and cell fate to control organ growth and regeneration. It promotes activation of the LATS kinases, which control gene expression by inhibiting the activity of the transcriptional co-activator proteins YAP and TAZ in mammals, or Yorkie in <i>Drosophila</i>. Diverse upstream inputs including both biochemical and biomechanical cues regulate Hippo signaling, which enable it to play a key role as a sensor of cells’ physical environment and an integrator of growth control signals. Several components of this pathway localize to cell-cell junctions, and contribute to regulation of Hippo signaling by cell polarity, cell contacts, and the cytoskeleton. Down-regulation of Hippo signaling promotes uncontrolled cell proliferation and impairs differentiation, and is associated with cancer. We review current understanding of Hippo signaling, highlighting progress in elucidating its regulatory mechanisms and biological functions. </p>