Crossref journal-article
American Society for Cell Biology (ASCB)
Molecular Biology of the Cell (1076)
Abstract

Cardiac contractility is regulated through the activity of various key Ca2+-handling proteins. The sarco(endo)plasmic reticulum (SR) Ca2+transport ATPase (SERCA2a) and its inhibitor phospholamban (PLN) control the uptake of Ca2+by SR membranes during relaxation. Recently, the antiapoptotic HS-1–associated protein X-1 (HAX-1) was identified as a binding partner of PLN, and this interaction was postulated to regulate cell apoptosis. In the current study, we determined that HAX-1 can also bind to SERCA2. Deletion mapping analysis demonstrated that amino acid residues 575–594 of SERCA2's nucleotide binding domain are required for its interaction with the C-terminal domain of HAX-1, containing amino acids 203-245. In transiently cotransfected human embryonic kidney 293 cells, recombinant SERCA2 was specifically targeted to the ER, whereas HAX-1 selectively concentrated at mitochondria. On triple transfections with PLN, however, HAX-1 massively translocated to the ER membranes, where it codistributed with PLN and SERCA2. Overexpression of SERCA2 abrogated the protective effects of HAX-1 on cell survival, after hypoxia/reoxygenation or thapsigargin treatment. Importantly, HAX-1 overexpression was associated with down-regulation of SERCA2 expression levels, resulting in significant reduction of apparent ER Ca2+levels. These findings suggest that HAX-1 may promote cell survival through modulation of SERCA2 protein levels and thus ER Ca2+stores.

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Vafiadaki, E., Arvanitis, D. A., Pagakis, S. N., Papalouka, V., Sanoudou, D., Kontrogianni-Konstantopoulos, A., & Kranias, E. G. (2009). The Anti-apoptotic Protein HAX-1 Interacts with SERCA2 and Regulates Its Protein Levels to Promote Cell Survival. Molecular Biology of the Cell, 20(1), 306–318.

Authors 7
  1. Elizabeth Vafiadaki (first)
  2. Demetrios A. Arvanitis (additional)
  3. Stamatis N. Pagakis (additional)
  4. Vasiliki Papalouka (additional)
  5. Despina Sanoudou (additional)
  6. Aikaterini Kontrogianni-Konstantopoulos (additional)
  7. Evangelia G. Kranias (additional)
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Dates
Type When
Created 16 years, 10 months ago (Oct. 29, 2008, 9:36 p.m.)
Deposited 2 years, 3 months ago (May 20, 2023, 4:36 p.m.)
Indexed 1 month, 1 week ago (July 22, 2025, 6:48 a.m.)
Issued 16 years, 8 months ago (Jan. 1, 2009)
Published 16 years, 8 months ago (Jan. 1, 2009)
Published Print 16 years, 8 months ago (Jan. 1, 2009)
Funders 0

None

@article{Vafiadaki_2009, title={The Anti-apoptotic Protein HAX-1 Interacts with SERCA2 and Regulates Its Protein Levels to Promote Cell Survival}, volume={20}, ISSN={1939-4586}, url={http://dx.doi.org/10.1091/mbc.e08-06-0587}, DOI={10.1091/mbc.e08-06-0587}, number={1}, journal={Molecular Biology of the Cell}, publisher={American Society for Cell Biology (ASCB)}, author={Vafiadaki, Elizabeth and Arvanitis, Demetrios A. and Pagakis, Stamatis N. and Papalouka, Vasiliki and Sanoudou, Despina and Kontrogianni-Konstantopoulos, Aikaterini and Kranias, Evangelia G.}, editor={Omary, M. Bishr}, year={2009}, month=jan, pages={306–318} }