Elucidation of a Universal Size-control Mechanism in Drosophila and Mammals

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2007 Sep 25

PMID 17889654

Citations 1270

Authors

Jixin Dong

Georg Feldmann

Jianbin Huang

Shian Wu

Nailing Zhang

Sarah A Comerford

Mariana F Gayyed

Robert A Anders

Anirban Maitra

Duojia Pan

Affiliations

Soon will be listed here.

Abstract

Coordination of cell proliferation and cell death is essential to attain proper organ size during development and for maintaining tissue homeostasis throughout postnatal life. In Drosophila, these two processes are orchestrated by the Hippo kinase cascade, a growth-suppressive pathway that ultimately antagonizes the transcriptional coactivator Yorkie (Yki). Here we demonstrate that a single phosphorylation site in Yki mediates the growth-suppressive output of the Hippo pathway. Hippo-mediated phosphorylation inactivates Yki by excluding it from the nucleus, whereas loss of Hippo signaling leads to nuclear accumulation and therefore increased Yki activity. We further delineate a mammalian Hippo signaling pathway that culminates in the phosphorylation of YAP, the mammalian homolog of Yki. Using a conditional YAP transgenic mouse model, we demonstrate that the mammalian Hippo pathway is a potent regulator of organ size, and that its dysregulation leads to tumorigenesis. These results uncover a universal size-control mechanism in metazoan.

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