hippo encodes a Ste-20 family protein kinase that restricts cell proliferation and promotes apoptosis in conjunction with salvador and warts

Shian Wu, Jianbin Huang, Jixin Dong, Duojia Pan

Research output: Contribution to journalArticle

680 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)445-456
Number of pages12
JournalCell
Volume114
Issue number4
DOIs
StatePublished - Aug 22 2003

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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