Mob as tumor suppressor is activated by Hippo kinase for growth inhibition in Drosophila
Open Access
- 8 March 2007
- journal article
- research article
- Published by Springer Nature in The EMBO Journal
- Vol. 26 (7) , 1772-1781
- https://doi.org/10.1038/sj.emboj.7601630
Abstract
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
This publication has 41 references indexed in Scilit:
- The Hippo Signaling Pathway Coordinately Regulates Cell Proliferation and Apoptosis by Inactivating Yorkie, the Drosophila Homolog of YAPCell, 2005
- Control of Cell Proliferation and Apoptosis by Mob as Tumor Suppressor, MatsCell, 2005
- The Drosophila Ste20 family kinase dMST functions as a tumor suppressor by restricting cell proliferation and promoting apoptosisGenes & Development, 2003
- Crystal Structure of a Human Mob1 ProteinPublished by Elsevier ,2003
- The Salvador partner Hippo promotes apoptosis and cell-cycle exit in DrosophilaNature Cell Biology, 2003
- Hippo promotes proliferation arrest and apoptosis in the Salvador/Warts pathwayNature Cell Biology, 2003
- The Drosophila Mst Ortholog, hippo, Restricts Growth and Cell Proliferation and Promotes ApoptosisCell, 2003
- hippo Encodes a Ste-20 Family Protein Kinase that Restricts Cell Proliferation and Promotes Apoptosis in Conjunction with salvador and wartsCell, 2003
- Shar-pei mediates cell proliferation arrest during imaginal disc growth inDrosophilaDevelopment, 2002
- salvador Promotes Both Cell Cycle Exit and Apoptosis in Drosophila and Is Mutated in Human Cancer Cell LinesCell, 2002