RT Journal Article
SR Electronic
T1 TRIP6 inhibits the Hippo signaling pathway in response to tension at adherens junctions
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 182204
DO 10.1101/182204
A1 Shubham Dutta
A1 Sebastian Mana-Capelli
A1 Murugan Paramasivam
A1 Ishani Dasgupta
A1 Heather Cirka
A1 Kris Billiar
A1 Dannel McCollum
YR 2017
UL http://biorxiv.org/content/early/2017/08/30/182204.abstract
AB The transcriptional co-activator YAP controls cell proliferation, survival, and tissue regeneration in response to changes in the mechanical environment. It is not known how mechanical stimuli such as tension are sensed and how the signal is transduced to control YAP activity. Here we show that the LIM domain protein TRIP6 acts as part of a mechanotransduction pathway at adherens junctions to promote YAP activity by inhibiting the LATS1/2 kinases. Previous studies showed that vinculin at adherens junctions becomes activated by mechanical tension. We show that vinculin inhibits Hippo signaling by recruiting TRIP6 to adherens junctions and stimulating its binding to and inhibition of LATS1/2 in response to tension. TRIP6 competes with MOB1 for binding to LATS1/2 thereby blocking MOB1 from recruiting the LATS1/2 activating kinases MST1/2. Together these findings reveal a novel mechanotransduction cascade that transduces tension signals sensed at adherens junctions to control Hippo pathway signaling.