The tumor suppressor WARTS activates the Omi/HtrA2-dependent pathway of cell death

Shinji Kuninaka, Masanobu Nomura, Toru Hirota, Shin Ichi Iida, Toshihiro Hara, Shinobu Honda, Naoko Kunitoku, Takashi Sasayama, Yoshimi Arima, Tomotoshi Marumoto, Kageharu Koja, Shin Yonehara, Hideyuki Saya

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39 Citations (Scopus)

Abstract

Drosophila tumor suppressor WARTS (Wts) is an evolutionally conserved serine/threonine kinase and parti cipates in a signaling complex that regulates both proliferation and apoptosis to ensure the proper size and shape of the fly. Human counterparts of this complex have been found to be frequently downregulated or mutated in cancers. WARTS, a human homolog of Wts, is also known as tumor suppressor and mitotic regulator, but its molecular implications in tumorigenesis are still obscure. Here, we show that WARTS binds via its C-terminus to the PDZ domain of a proapoptotic serine protease Omi/ HtrA2. Depletion of WARTS inhibited Omi/HtrA2-mediated cell death, whereas overexpression of WARTS promoted this process. Furthermore, WARTS can enhance the protease activity of Omi/HtrA2 both in vivo and in vitro. Activation of Omi/HtrA2-mediated cell death is thus a potential mechanism for the tumor suppressive activity of WARTS.

Original languageEnglish
Pages (from-to)5287-5298
Number of pages12
JournalOncogene
Volume24
Issue number34
DOIs
Publication statusPublished - 2005 Aug 11
Externally publishedYes

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Keywords

  • Apoptosis
  • Cancer
  • Caspases
  • IAPs
  • Mitochondria
  • Mitotic kinases
  • PDZ domain

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Kuninaka, S., Nomura, M., Hirota, T., Iida, S. I., Hara, T., Honda, S., Kunitoku, N., Sasayama, T., Arima, Y., Marumoto, T., Koja, K., Yonehara, S., & Saya, H. (2005). The tumor suppressor WARTS activates the Omi/HtrA2-dependent pathway of cell death. Oncogene, 24(34), 5287-5298. https://doi.org/10.1038/sj.onc.1208682