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Regulation and crosstalk

Nature Reviews Cancer volume 10, pages 386–387 (2010)Cite this article

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Helena Richardson and colleagues had previously noted that loss-of-function of the tumour suppressor Lethal (2) giant larvae (L2GL) in the developing eye of Drosophila melanogaster results in aberrant proliferation and cell survival. A similar effect is also seen when atypical protein kinase C (aPKC) or Crumbs (CRB) are overexpressed. L2GL, aPKC and CRB regulate apicobasal polarity, so their effect on proliferation and survival was intriguing. Further examination of the loss of l2gl expression or overexpression of aPKC or Crb in eye epithelial cells showed increased expression of genes that are targets of the transcription co-activator Yorkie (YKI), the activity of which is suppressed by the SAV–WTS–HPO kinase pathway. So, why is the HPO pathway inactive in cells that have lost L2GL expression? HPO and Ras-associated domain family protein (RASSF) are mislocalized, with both present in the basal region of the cell. RASSF competes with SAV for HPO binding and so functions as an inhibitor of HPO. L2GL and aPKC work in opposition to one another, explaining why the loss of one and overexpression of the other induces the same phenotype. However, overexpression of Crb resulted in the mislocalization of the FERM domain protein Expanded (EX), a known regulator of the HPO pathway.

these papers uncover more molecular links between cell polarity, cell division and cell fate.

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ORIGINAL RESEARCH PAPERS

  1. Greschik, N. A. et al. Lgl, aPKC and crumbs regulate the salvador/warts/hippo pathway through two distinct mechanisms. Curr. Biol. 20, 573–581 (2010)

    Article  Google Scholar 

  2. Robinson, B. S., Huang, J., Hong, Y. & Moberg, K. H. Crumbs regulates salvador/warts/hippo signaling in Drosophila via the FERM-domain protein Expanded. Curr. Biol. 20, 582–590 (2010)

    Article  CAS  Google Scholar 

  3. Varelas, X. et al. The hippo pathway regulates Wnt/b-catenin signaling. Dev. Cell 18, 579–591 (2010)

    Article  CAS  Google Scholar 

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Authors
  1. Nicola McCarthy
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McCarthy, N. Regulation and crosstalk. Nat Rev Cancer 10, 386–387 (2010). https://doi.org/10.1038/nrc2864

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  • DOI: https://doi.org/10.1038/nrc2864

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