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Foundation NF2 Young Investigator Finds Dual Role for Human ‘Hippo’

By March 11, 2010December 18th, 2023Awareness, NF2-SWN, Science & Research

New research* (links to free full paper) published by Children’s Tumor Foundation Young Investigator Awardee Geoffrey Kilili and his mentor Dr. John Kyriakis at Tufts University have uncovered novel ideas about the signaling pathways of merlin, the tumor suppressor protein made by the NF2 gene. In the fruit fly, merlin protein function acts by promoting a cell signaling element called Hippo. In mammalian cells (e.g. mice and humans) Hippo is called Mst2 and as in flies mediates merlin tumor suppressor function/prevention of excess cell proliferation; Mst2 itself is negatively regulated by another cell signaling element, called Raf-1.  Setting out to better understand the interactions between merlin, Mst2 and Raf-1 in mammalian cells, Kilili and Kyriakis surprisingly found out that unlike in fly, merlin did not necessarily promote Mst2 signaling; and, surprisingly, inhibiting Mst2 impairs Raf-1 signaling, after which cell proliferation ceases. This research reveals a potentially more complex role for Mst2 than previously thought, perhaps dual roles for Mst2 as a tumor suppressor and as a cell growth promoter.  This research was supported by an NIH Grant to Dr. Kyriakis, Mr. Kilili was supported by a Children’s Tumor Foundation 2008-2010 Young Investigator Award.