File:Hippo pathway on-off cartoon.jpg: Difference between revisions
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Revision as of 09:01, 21 March 2018
The Hippo Pathway and its mode of action
- A - When the Hippo pathway is ON, MST1/2 phosphorylate SAV1 and together they phosphorylate and activate MOB1A/B and LATS1/2, which then phosphorylate YAP and TAZ. Phosphorylated YAP and TAZ are sequestered in the cytoplasm by the 14-3-3 phosphopeptide binding proteins and shunted for proteasomal degradation. As a result, the TEAD transcription factors associate with VGL4 and suppress target gene expression.
- B - When the Hippo pathway is OFF, the MST1/2 and LATS1/2 kinases are inactive, YAP and TAZ are not phosphorylated and accumulate in the nucleus where they displace VGL4 and complex with TEADs. YAP and TAZ are transcriptional co-activators and in complex with TEADs promote the expression of target genes.
Reference
Johnson R & Halder G. (2014). The two faces of Hippo: targeting the Hippo pathway for regenerative medicine and cancer treatment. Nat Rev Drug Discov , 13, 63-79. PMID: 24336504 DOI.
Copyright
Reprinted by permission from Macmillan Publishers Ltd: Nature Reviews Drug Discovery (Randy Johnson, Georg Halder The two faces of Hippo: targeting the Hippo pathway for regenerative medicine and cancer treatment. Nat Rev Drug Discov: 2014, 13(1);63-79), copyright (2015)
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