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Subcellular localization determines the delicate balance between the anti- and pro-apoptotic activity of Livin

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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.

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Abbreviations

IAP:

inhibitor of apoptosis

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Acknowledgments

We thank D. Rund for critical reading of the manuscript. We thank M Tharshis. This work was supported by the Caesarea Edmond Benjamin De Rothschild Foundation.

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Authors and Affiliations

  1. Department of Hematology, Hadassah - Hebrew University Medical Center, P.O.B. 12000, Jerusalem, 91120, Israel

    Boaz Nachmias, Itay Lazar, Meital Elmalech, Ihab Abed-El-Rahaman, Yaqoub Asshab, Riki Perlman & Dina Ben-Yehuda

  2. Hebrew University - Hadassah Medical School, Jerusalem, Israel

    Boaz Nachmias & Itay Lazar

  3. Lautenberg Center for General and Tumor Immunology, Hebrew University - Hadassah Medical School, Jerusalem, Israel

    Ofer Mandelboim

Authors
  1. Boaz Nachmias
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  2. Itay Lazar
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  8. Dina Ben-Yehuda
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Correspondence to Dina Ben-Yehuda.

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Nachmias, B., Lazar, I., Elmalech, M. et al. Subcellular localization determines the delicate balance between the anti- and pro-apoptotic activity of Livin. Apoptosis 12, 1129–1142 (2007). https://doi.org/10.1007/s10495-006-0049-1

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  • DOI: https://doi.org/10.1007/s10495-006-0049-1

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