Skip to main content
Article thumbnail
Location of Repository

Control of Tissue Growth and Cell Transformation by the Salvador/Warts/Hippo Pathway

By Xiaomeng Zhang, Felix A. Grusche and Kieran F. Harvey


The Salvador-Warts-Hippo (SWH) pathway is an important regulator of tissue growth that is frequently subverted in human cancer. The key oncoprotein of the SWH pathway is the transcriptional co-activator, Yes-associated protein (YAP). YAP promotes tissue growth and transformation of cultured cells by interacting with transcriptional regulatory proteins via its WW domains, or, in the case of the TEAD1-4 transcription factors, an N-terminal binding domain. YAP possesses a putative transactivation domain in its C-terminus that is necessary to stimulate transcription factors in vitro, but its requirement for YAP function has not been investigated in detail. Interestingly, whilst the WW domains and TEAD-binding domain are highly conserved in the Drosophila melanogaster YAP orthologue, Yorkie, the majority of the C-terminal region of YAP is not present in Yorkie. To investigate this apparent conundrum, we assessed the functional roles of the YAP and Yorkie C-termini. We found that these regions were not required for Yorkie's ability to drive tissue growth in vivo, or YAP's ability to promote anchorage-independent growth or resistance to contact inhibition. However, the YAP transactivation domain was required for YAP's ability to induce cell migration and invasion. Moreover, a role for the YAP transactivation domain in cell transformation was uncovered when the YAP WW domains were mutated together with the transactivation domain. This shows that YAP can promote cell transformation in a flexible manner, presumably by contacting transcriptional regulatory proteins either via its WW domains or its transactivation domain

Topics: Research Article
Publisher: Public Library of Science
OAI identifier:
Provided by: PubMed Central

Suggested articles


  1. (2010). A coordinated phosphorylation by Lats and CK1 regulates YAP stability through SCF(betaTRCP).
  2. (1999). A WW domaincontaining yes-associated protein (YAP) is a novel transcriptional co-activator.
  3. (2009). Both TEAD-binding and WW domains are required for the growth stimulation and oncogenic transformation activity of yes-associated protein.
  4. (2011). Cooperative regulation of growth by Yorkie and Mad through bantam.
  5. (2007). Elucidation of a universal size-control mechanism in Drosophila and mammals.
  6. (2010). Hippo pathway effector Yap is an ovarian cancer oncogene.
  7. (2011). Hippo signaling: growth control and beyond.
  8. (2006). Identification and validation of oncogenes in liver cancer using an integrative oncogenomic approach.
  9. (2007). Inactivation of YAP oncoprotein by the Hippo pathway is involved in cell contact inhibition and tissue growth control.
  10. (2008). Loss of human Scribble cooperates with H-Ras to promote cell invasion through deregulation of MAPK signalling.
  11. (2008). Mammalian Tead proteins regulate cell proliferation and contact inhibition as transcriptional mediators of Hippo signaling.
  12. (1999). Mosaic analysis with a repressible cell marker for studies of gene function in neuronal morphogenesis.
  13. (2009). Nuclear localization and pro-apoptotic signaling of YAP2 require intact PDZ-binding motif.
  14. (2010). Overexpression of yesassociated protein contributes to progression and poor prognosis of non-smallcell lung cancer.
  15. (2012). Premetazoan Origin of the Hippo Signaling Pathway.
  16. (2002). salvador Promotes both cell cycle exit and apoptosis in Drosophila and is mutated in human cancer cell lines.
  17. (2008). SCALLOPED interacts with YORKIE, the nuclear effector of the hippo tumorsuppressor pathway in Drosophila.
  18. (2008). TEAD mediates YAP-dependent gene induction and growth control.
  19. (2001). TEAD/TEF transcription factors utilize the activation domain of YAP65, a Src/Yesassociated protein localized in the cytoplasm.
  20. (2011). The Evolutionary history of YAP and the Hippo/YAP pathway. Mol Biol Evol;doi:
  21. (2011). The Hippo pathway transcriptional co-activator, YAP, is an ovarian cancer oncogene.
  22. (2005). The Hippo signaling pathway coordinately regulates cell proliferation and apoptosis by inactivating Yorkie, the Drosophila Homolog of YAP.
  23. (2010). The hippo signaling pathway in development and cancer.
  24. (2007). The Salvador-Warts-Hippo pathway - an emerging tumour-suppressor network.
  25. (2011). The Salvador/ Warts/Hippo pathway controls regenerative tissue growth in Drosophila melanogaster.
  26. (2008). The TEAD/TEF family of transcription factor Scalloped mediates Hippo signaling in organ size control.
  27. (2008). The TEAD/TEF family protein Scalloped mediates transcriptional output of the Hippo growth-regulatory pathway.
  28. (2009). Transcriptional output of the Salvador/warts/hippo pathway is controlled in distinct fashions in Drosophila melanogaster and mammalian cell lines.
  29. (2006). Transforming properties of YAP, a candidate oncogene on the chromosome 11q22 amplicon.
  30. (2010). Upstream regulation of the hippo size control pathway.
  31. (2011). Wbp2 cooperates with Yorkie to drive tissue growth downstream of the Salvador-Warts-Hippo pathway.
  32. (2011). WW domain-mediated interaction with Wbp2 is important for the oncogenic property of TAZ.
  33. (2007). YAP1 increases organ size and expands undifferentiated progenitor cells.
  34. (1994). Yes-associated protein (YAP65) is a proline-rich phosphoprotein that binds to the SH3 domain of the Yes proto-oncogene product.
  35. (2009). Yes-associated protein is an independent prognostic marker in hepatocellular carcinoma.

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.