TY - JOUR
T1 - hippo encodes a Ste-20 family protein kinase that restricts cell proliferation and promotes apoptosis in conjunction with salvador and warts
AU - Wu, Shian
AU - Huang, Jianbin
AU - Dong, Jixin
AU - Pan, Duojia
N1 - Funding Information:
We apologize for deleting several references due to space limitation. We would like to thank Bruce Edgar and Keith Wharton for critical reading of the manuscript, and Hugo Bellen, Wei Du, Iswar Hariharan, Bruce Hay, Christian Lehner, Terry Orr-Weaver, Helena Richardson, and Hermann Steller for various reagents. D.J.P. is a Virginia Murchison Linthicum Endowed Scholar in Medical Science and is supported by grants from NIH (GM62323), American Heart Association (0130222N), and American Cancer Society (RSG0303601DDC).
PY - 2003/8/22
Y1 - 2003/8/22
N2 - The coordination between cell proliferation and cell death is essential to maintain homeostasis within multicellular organisms. The mechanisms underlying this regulation are yet to be completely understood. Here, we report the identification of hippo (hpo) as a gene that regulates both cell proliferation and cell death in Drosophila. hpo encodes a Ste-20 family protein kinase that binds to and phosphorylates the tumor suppressor protein Salvador (Sav), which is known to interact with the Warts (Wts) protein kinase. Loss of hpo results in elevated transcription of the cell cycle regulator cyclin E and the cell-death inhibitor diap1, leading to increased proliferation and reduced apoptosis. Further, we show that hpo, sav, and wts define a pathway that regulates diap1 at the transcriptional level. A human homolog of hpo completely rescues the overgrowth phenotype of Drosophila hpo mutants, suggesting that hpo might play a conserved role for growth control in mammals.
AB - The coordination between cell proliferation and cell death is essential to maintain homeostasis within multicellular organisms. The mechanisms underlying this regulation are yet to be completely understood. Here, we report the identification of hippo (hpo) as a gene that regulates both cell proliferation and cell death in Drosophila. hpo encodes a Ste-20 family protein kinase that binds to and phosphorylates the tumor suppressor protein Salvador (Sav), which is known to interact with the Warts (Wts) protein kinase. Loss of hpo results in elevated transcription of the cell cycle regulator cyclin E and the cell-death inhibitor diap1, leading to increased proliferation and reduced apoptosis. Further, we show that hpo, sav, and wts define a pathway that regulates diap1 at the transcriptional level. A human homolog of hpo completely rescues the overgrowth phenotype of Drosophila hpo mutants, suggesting that hpo might play a conserved role for growth control in mammals.
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U2 - 10.1016/S0092-8674(03)00549-X
DO - 10.1016/S0092-8674(03)00549-X
M3 - Article
C2 - 12941273
AN - SCOPUS:0042232429
SN - 0092-8674
VL - 114
SP - 445
EP - 456
JO - Cell
JF - Cell
IS - 4
ER -