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SUMMARY:Metabolic Control of YAP and TAZ by the Mevalonate Pathway
DTSTART:20160829T093000
DTEND:20160829T103000
DTSTAMP:20260916T044015Z
UID:cdf81d5e3687c8ace403ff9c9c82f0ea9510ea6f5c5c77e7d7866555
CATEGORIES:Conferences - Seminars
DESCRIPTION:Dr. Giovanni Sorrentino\, National Laboratory CIB\, Area Scien
 ce Park\, Trieste (Italy)\nSEMINAR of the LAUSANNE INTEGRATIVE METABOLISM 
 and NUTRITION ALLIANCE (LIMNA)Abstract:\nThe YAP and TAZ mediators of the 
 Hippo pathway promote tissue proliferation\, organ growth and cancer devel
 opment. However\, how their biological properties intersect with cellular 
 metabolism remains unexplained. In our recent work\, we show that YAP/TAZ 
 activity is controlled by the SREBP/mevalonate pathway. Inhibition of the 
 rate-limiting enzyme of this pathway (HMG-CoA reductase) by statins oppose
 s YAP/TAZ nuclear localization and transcriptional responses.\nMechanistic
 ally\, the geranylgeranyl pyrophosphate produced by the mevalonate cascade
  is required for activation of Rho GTPases that\, in turn\, activate YAP/T
 AZ by inhibiting their phosphorylation and promoting their nuclear accumul
 ation. In Drosophila melanogaster\, inhibition of mevalonate biosynthesis 
 and geranylgeranylation blunts the eye overgrowth induced by Yorkie\, the 
 YAP/TAZ orthologue. In tumour cells\, YAP/TAZ activation is promoted by in
 creased levels of mevalonic acid produced by SREBP transcriptional activit
 y\, which is induced by its oncogenic cofactor mutant p53.\nThese findings
  reveal an additional layer of YAP/TAZ regulation by metabolic cues.
LOCATION:AI 1 153 http://map.epfl.ch/?room=ai1153
STATUS:CONFIRMED
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