TY - JOUR
T1 - The Hippo signaling pathway coordinately regulates cell proliferation and apoptosis by inactivating Yorkie, the Drosophila homolog of YAP
AU - Huang, Jianbin
AU - Wu, Shian
AU - Barrera, Jose
AU - Matthews, Krista
AU - Pan, Duojia
N1 - Funding Information:
We would like to thank Elizabeth Chen and Keith Wharton for critical reading of the manuscript and Bruce Hay, Albert Courey, Kent Golic, Terry Orr-Weaver, Helena Richardson, and Hermann Steller for providing various reagents. D.J.P. was supported by the Endowed Scholars Program while at UT Southwestern. This work was supported by grants from the National Institutes of Health to D.J.P.
PY - 2005/8/12
Y1 - 2005/8/12
N2 - Coordination between cell proliferation and cell death is essential to maintain homeostasis in multicellular organisms. In Drosophila, these two processes are regulated by a pathway involving the Ste20-like kinase Hippo (Hpo) and the NDR family kinase Warts (Wts; also called Lats). Hpo phosphorylates and activates Wts, which in turn, through unknown mechanisms, negatively regulates the transcription of cell-cycle and cell-death regulators such as cycE and diap1. Here we identify Yorkie (Yki), the Drosophila ortholog of the mammalian transcriptional coactivator yes-associated protein (YAP), as a missing link between Wts and transcriptional regulation. Yki is required for normal tissue growth and diap1 transcription and is phosphorylated and inactivated by Wts. Overexpression of yki phenocopies loss-of-function mutations of hpo or wts, including elevated transcription of cycE and diap1, increased proliferation, defective apoptosis, and tissue overgrowth. Thus, Yki is a critical target of the Wts/Lats protein kinase and a potential oncogene.
AB - Coordination between cell proliferation and cell death is essential to maintain homeostasis in multicellular organisms. In Drosophila, these two processes are regulated by a pathway involving the Ste20-like kinase Hippo (Hpo) and the NDR family kinase Warts (Wts; also called Lats). Hpo phosphorylates and activates Wts, which in turn, through unknown mechanisms, negatively regulates the transcription of cell-cycle and cell-death regulators such as cycE and diap1. Here we identify Yorkie (Yki), the Drosophila ortholog of the mammalian transcriptional coactivator yes-associated protein (YAP), as a missing link between Wts and transcriptional regulation. Yki is required for normal tissue growth and diap1 transcription and is phosphorylated and inactivated by Wts. Overexpression of yki phenocopies loss-of-function mutations of hpo or wts, including elevated transcription of cycE and diap1, increased proliferation, defective apoptosis, and tissue overgrowth. Thus, Yki is a critical target of the Wts/Lats protein kinase and a potential oncogene.
UR - http://www.scopus.com/inward/record.url?scp=23744458034&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=23744458034&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2005.06.007
DO - 10.1016/j.cell.2005.06.007
M3 - Article
C2 - 16096061
AN - SCOPUS:23744458034
SN - 0092-8674
VL - 122
SP - 421
EP - 434
JO - Cell
JF - Cell
IS - 3
ER -