Abstract
Livin is a member of the Inhibitor of Apoptosis Protein family which inhibits apoptosis induced by a variety of stimuli. We previously identified Livin and demonstrated that following apoptotic stimuli, Livin is cleaved by effector caspases to produce a truncated form with paradoxical pro-apoptotic activity. In the present study, we reveal that while full-length Livin shows diffuse cytoplasmic localization, truncated Livin (tLivin) is found in a peri-nuclear distribution with marked localization to the Golgi apparatus. Using mutation analysis, we identified two domains that are crucial for the pro-apoptotic activity of tLivin: the N-terminal region of tLivin which is exposed by cleavage, and the RING domain. We demonstrate that, of the N-terminal sequence, only the first N-terminal glycine residue dictates the peri-nuclear distribution of tLivin. However, while the perinuclear localization of tLivin is essential, it is not sufficient for tLivin to exert its pro-apoptotic function. Once tLivin is properly localized, an intact RING domain enables its pro-apoptotic function.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / chemistry
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Adaptor Proteins, Signal Transducing / genetics
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Adaptor Proteins, Signal Transducing / isolation & purification
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Adaptor Proteins, Signal Transducing / metabolism*
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Amino Acid Sequence
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Apoptosis / drug effects
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Apoptosis / physiology*
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Caspases / metabolism
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Cell Line
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Cell Nucleus / metabolism
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Cytoplasm / metabolism*
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Golgi Apparatus / metabolism*
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Humans
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Inhibitor of Apoptosis Proteins / chemistry
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Inhibitor of Apoptosis Proteins / genetics
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Inhibitor of Apoptosis Proteins / isolation & purification
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Inhibitor of Apoptosis Proteins / metabolism*
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Molecular Sequence Data
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Mutation
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Neoplasm Proteins / chemistry
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Neoplasm Proteins / genetics
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Neoplasm Proteins / isolation & purification
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Neoplasm Proteins / metabolism*
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Protein Isoforms / chemistry
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Protein Isoforms / metabolism
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Sequence Alignment
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Structure-Activity Relationship
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Transfection
Substances
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Adaptor Proteins, Signal Transducing
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BIRC7 protein, human
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Inhibitor of Apoptosis Proteins
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Neoplasm Proteins
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Protein Isoforms
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Caspases