The anti-apoptotic protein HAX-1 interacts with SERCA2 and regulates Its protein levels to promote cell survival

Elizabeth Vafiadaki, Demetrios A. Arvanitis, Stamatis N. Pagakis, Vasiliki Papalouka, Despina Sanoudou, Aikaterini Kontrogianni-Konstantopoulos, Evangelia G. Kranias

Research output: Contribution to journalArticle

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Abstract

Cardiac contractility is regulated through the activity of various key Ca 2+-handling proteins. The sarco(endo)plasmic reticulum (SR) Ca 2+ transport ATPase (SERCA2a) and its inhibitor phospholamban (PLN) control the uptake of Ca 2+ 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 Ca 2+ levels. These findings suggest that HAX-1 may promote cell survival through modulation of SERCA2 protein levels and thus ER Ca 2+ stores.

Original languageEnglish
Pages (from-to)306-318
Number of pages13
JournalMolecular Biology of the Cell
Volume20
Issue number1
DOIs
Publication statusPublished - 1 Jan 2009
Externally publishedYes

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Apoptosis Regulatory Proteins
Cell Survival
Proteins
Amino Acids
Reticulum
Thapsigargin
Membranes
Transfection
Adenosine Triphosphatases
Mitochondria
Down-Regulation
Nucleotides
Apoptosis
Kidney

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

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. https://doi.org/10.1091/mbc.E08-06-0587

The anti-apoptotic protein HAX-1 interacts with SERCA2 and regulates Its protein levels to promote cell survival. / Vafiadaki, Elizabeth; Arvanitis, Demetrios A.; Pagakis, Stamatis N.; Papalouka, Vasiliki; Sanoudou, Despina; Kontrogianni-Konstantopoulos, Aikaterini; Kranias, Evangelia G.

In: Molecular Biology of the Cell, Vol. 20, No. 1, 01.01.2009, p. 306-318.

Research output: Contribution to journalArticle

Vafiadaki, E, Arvanitis, DA, Pagakis, SN, Papalouka, V, Sanoudou, D, Kontrogianni-Konstantopoulos, A & Kranias, EG 2009, 'The anti-apoptotic protein HAX-1 interacts with SERCA2 and regulates Its protein levels to promote cell survival', Molecular Biology of the Cell, vol. 20, no. 1, pp. 306-318. https://doi.org/10.1091/mbc.E08-06-0587
Vafiadaki E, Arvanitis DA, Pagakis SN, Papalouka V, Sanoudou D, Kontrogianni-Konstantopoulos A et al. The anti-apoptotic protein HAX-1 interacts with SERCA2 and regulates Its protein levels to promote cell survival. Molecular Biology of the Cell. 2009 Jan 1;20(1):306-318. https://doi.org/10.1091/mbc.E08-06-0587
Vafiadaki, Elizabeth ; Arvanitis, Demetrios A. ; Pagakis, Stamatis N. ; Papalouka, Vasiliki ; Sanoudou, Despina ; Kontrogianni-Konstantopoulos, Aikaterini ; Kranias, Evangelia G. / The anti-apoptotic protein HAX-1 interacts with SERCA2 and regulates Its protein levels to promote cell survival. In: Molecular Biology of the Cell. 2009 ; Vol. 20, No. 1. pp. 306-318.
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