Metabolic Control of YAP and TAZ by the Mevalonate Pathway
Event details
| Date | 29.08.2016 |
| Hour | 09:30 › 10:30 |
| Speaker | Dr. Giovanni Sorrentino, National Laboratory CIB, Area Science Park, Trieste (Italy) |
| Location | |
| Category | Conferences - Seminars |
SEMINAR of the LAUSANNE INTEGRATIVE METABOLISM and NUTRITION ALLIANCE (LIMNA)
Abstract:
The YAP and TAZ mediators of the Hippo pathway promote tissue proliferation, organ growth and cancer development. 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 opposes YAP/TAZ nuclear localization and transcriptional responses.
Mechanistically, the geranylgeranyl pyrophosphate produced by the mevalonate cascade is required for activation of Rho GTPases that, in turn, activate YAP/TAZ by inhibiting their phosphorylation and promoting their nuclear accumulation. 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 increased levels of mevalonic acid produced by SREBP transcriptional activity, which is induced by its oncogenic cofactor mutant p53.
These findings reveal an additional layer of YAP/TAZ regulation by metabolic cues.
Abstract:
The YAP and TAZ mediators of the Hippo pathway promote tissue proliferation, organ growth and cancer development. 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 opposes YAP/TAZ nuclear localization and transcriptional responses.
Mechanistically, the geranylgeranyl pyrophosphate produced by the mevalonate cascade is required for activation of Rho GTPases that, in turn, activate YAP/TAZ by inhibiting their phosphorylation and promoting their nuclear accumulation. 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 increased levels of mevalonic acid produced by SREBP transcriptional activity, which is induced by its oncogenic cofactor mutant p53.
These findings reveal an additional layer of YAP/TAZ regulation by metabolic cues.
Practical information
- Informed public
- Free
Organizer
- Prof. Kristina Schoonjans for the Lausanne Integrative Metabolism and Nutrition Alliance (LIMNA)
Contact
- Prof. Kristina Schoonjans
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