Subcellular localization determines the delicate balance between the anti- and pro-apoptotic activity of Livin |
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Authors: | Boaz Nachmias Itay Lazar Meital Elmalech Ihab Abed-El-Rahaman Yaqoub Asshab Ofer Mandelboim Riki Perlman Dina Ben-Yehuda |
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Institution: | (1) Department of Hematology, Hadassah - Hebrew University Medical Center, P.O.B. 12000, Jerusalem, 91120, Israel;(2) Hebrew University - Hadassah Medical School, Jerusalem, Israel;(3) Lautenberg Center for General and Tumor Immunology, Hebrew University - Hadassah Medical School, Jerusalem, Israel |
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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.
Electronic Supplementary Material Supplementary material is available in the online version of this article at . |
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Keywords: | Apoptosis IAPs Livin Subcellular localization Golgi apparatus RING domain |
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