Differential regulation of the apoptotic machinery during megakaryocyte differentiation and platelet production by inhibitor of apoptosis protein Livin

I. Abd-Elrahman, V. Deutsch, M. Pick, S. Kay, T. Neuman, R. Perlman, D. Ben-Yehuda*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


Livin is a member of the inhibitor of apoptosis proteins (IAP) family of intracellular antiapoptotic proteins that act by binding and inhibiting caspases. Upon strong apoptotic stimuli, it is then specifically cleaved by caspases to produce a truncated protein (tLivin) with a paradoxical proapoptotic activity. Intriguingly, we have detected robust protein levels of Livin in normal mature bone marrow megakaryocyte (MK) and platelets. To evaluate the potential role of Livin in thrombopoiesis, we used the human BCR-ABL+ cell line, LAMA-84, and cord blood CD34+ cells to induce differentiation toward MKs. Upon differentiation, induced by phorbol myristate acetate and concurrent with increase in Livin protein expression, LAMA-84 cells formed functional plateletlike particles. Livin overexpression in CD34+ progenitor cells induced higher endoreplication in the MKs generated. Furthermore, overexpression of Livin increased the ability of both primary MKs and differentiated LAMA-84 cells to produce functional platelets. In the differentiated LAMA-84 cells, we observed accumulation of proapoptotic tLivin concomitant with increased caspase-3 activity. Downregulation of Livin with small interfering RNA in both leukemic and primary MK cells decreased their ability to produce functional platelets. We suggest that Livin has a role in thrombopoiesis by regulating the apoptotic and antiapoptotic balance in MK endoreplication and platelet production.

Original languageAmerican English
Article numbere937
JournalCell Death and Disease
Issue number11
StatePublished - Nov 2013
Externally publishedYes

Bibliographical note

Funding Information:
Acknowledgements. We thank Shoshana Baron for assistance with flow cytometry, Eti Zwang for performing platelet function assays and Adi Loya for cloning the LAMA-84 cells. We also thank David Varon’s lab. This work was supported by Israel Science Foundation Grant 524/06 and the Gabrielle Rich Leukemia Foundation. IA is a recipient of The Israeli Ministry of Science, PhD scholarship for Israeli Citizens of Arab, Circassian and Druze descent.


  • Apoptosis
  • Inhibitor of apoptosis proteins
  • Livin
  • Megakaryocyte differentiation
  • Thrombopoiesis
  • tLivin


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