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ƒ^ƒCƒgƒ‹GWARTS tumor suppressor is a cellular target for mitochondrial serine protease Omi/HtrA2: A role of WARTS in caspase-independent cell death
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AbstractG
@Serine protease Omi/HtrA2 is released as an NH2-terminally removed mature form from mitochondria to the cytoplasm following apoptotic stimuli. Mature Omi can induce cell death in a caspase-independent manner via its protease activity. However, both the activation mechanism and physiological substrates of Omi protease are not yet clear. Here, we report that the tumor suppressor WARTS binds to the Omi PDZ domain through its COOH-terminus, and is a physiological substrate for Omi protease. The interaction is required for Omi to proteolyze WARTS. Reduction of WARTS expression by RNA interference significantly inhibits Omi-mediated caspase-independent cell death. Conversely, overexpression of WARTS augments the mature Omi-induced cell death. Thus, WARTS plays a role in activation of Omi-mediated cell death pathway.
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