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  • The EMBO Journal (2007) 26, 1772 - 1781
  • doi:10.1038/sj.emboj.7601630

Published online: 8 March 2007

Mob as tumor suppressor is activated by Hippo kinase for growth inhibition in Drosophila

Xiaomu Wei1, Takeshi Shimizu2 and Zhi-Chun Lai1,2,3

  1. Intercollege Graduate Program in Genetics, The Pennsylvania State University, University Park, PA, USA
  2. Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA, USA
  3. Department of Biology, The Pennsylvania State University, University Park, PA, USA

Correspondence to:

Zhi-Chun Lai, Intercollege Graduate Program in Genetics, The Pennsylvania State University, 201 LSB, University Park, PA 16802, USA. Tel.: +1 814 863 0479; Fax: +1 814 863 1357; E-mail: zcl1@psu.edu

Received 25 June 2006; Accepted 2 February 2007

Tissue growth and organ size are determined by coordinated cell proliferation and apoptosis in development. Recent studies have demonstrated that Hippo (Hpo) signaling plays a crucial role in coordinating these processes by restricting cell proliferation and promoting apoptosis. Here we provide evidence that the Mob as tumor suppressor protein, Mats, functions as a key component of the Hpo signaling pathway. We found that Mats associates with Hpo in a protein complex and is a target of the Hpo serine/threonine protein kinase. Mats phosphorylation by Hpo increases its affinity with Warts (Wts)/large tumor suppressor (Lats) serine/threonine protein kinase and ability to upregulate Wts catalytic activity to target downstream molecules such as Yorkie (Yki). Consistently, our epistatic analysis suggests that mats acts downstream of hpo. Coexpression analysis indicated that Mats can indeed potentiate Hpo-mediated growth inhibition in vivo. Our results support a model in which Mats is activated by Hpo through phosphorylation for growth inhibition, and this regulatory mechanism is conserved from flies to mammals.

  • Keywords:

    • Drosophila,
    • growth inhibition and tumor suppression,
    • hippo,
    • mats,
    • wts