The tumor suppressor WARTS activates the Omi / HtrA2-dependent pathway of cell death
| Autor: | Tomotoshi Marumoto, Toshihiro Hara, Shin Yonehara, Shinobu Honda, Yoshimi Arima, Naoko Kunitoku, Masanobu Nomura, Shin Ichi Iida, Shinji Kuninaka, Toru Hirota, Hideyuki Saya, Takashi Sasayama, Kageharu Koja |
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| Rok vydání: | 2005 |
| Předmět: |
High-Temperature Requirement A Serine Peptidase 2
Cancer Research Programmed cell death Tumor suppressor gene PDZ domain Apoptosis Protein Serine-Threonine Kinases Transfection medicine.disease_cause Mitochondrial Proteins Cytosol Genetics medicine Humans Molecular Biology Mitosis Cells Cultured Caspase biology Kinase Tumor Suppressor Proteins Serine Endopeptidases fungi virus diseases Virology Mitochondria Cancer research biology.protein Carcinogenesis |
| Zdroj: | Oncogene. 24:5287-5298 |
| ISSN: | 1476-5594 0950-9232 |
| DOI: | 10.1038/sj.onc.1208682 |
| Popis: | Drosophila tumor suppressor WARTS (Wts) is an evolutionally conserved serine / threonine kinase and participates 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. |
| Databáze: | OpenAIRE |
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