- Short Communication
- Open Access
Co-involvement of the mitochondria and endoplasmic reticulum in cell death induced by the novel ertargeted protein HAP
Cellular & Molecular Biology Letters volume 11, pages249–255 (2006)
HAP (a homologue of the ASY/Nogo-B protein), a novel human apoptosis-inducing protein, was found to be identical to RTN3. In an earlier study, we demonstrated that HAP localized exclusively to the endoplasmic reticulum (ER) and that its overexpression could induce cell apoptosis via a depletion of endoplasmic reticulum (ER) Ca2+ stores. In this study, we show that overexpression of HAP causes the activation of caspase-12 and caspase-3. We still detected the collapse of mitochondrial membrane potential (Δωm) and the release of cytochrome c in HAP-overexpressing HeLa cells. All the results indicate that both the mitochondria and the ER are involved in apoptosis caused by HAP overexpression, and suggest that HAP overexpression may initiate an ER overload response (EOR) and bring about the downstream apoptotic events.
Li, Q., Qi, B., Oka, K. and Shimakage, M. Link of a new type of apoptosis-inducing gene ASY/Nogo-B to human cancer. Oncogene 20 (2001) 3929–3936
Qi, B. and Qi, Y.P. Sci. China (Series C). 43 (2000) 310–320.
Qu, X.L., Qi, Y.P. and Qi, B. Generation of multiple mRNA transcripts from the novel human apoptosis-inducing gene hap by alternative polyadenylation utilization and the translational activation function of 3′ untranslated region. Arch. Biochem. Biophys. 400 (2002) 233–244.
Qi, B., Qi, Y.P., Liu, Q.Z. and Qu, X.L. A new type of apoptosis inducing gene Chin. Sci. Bull. 46 (2001) 1409–1411.
Sambrook, J.F. The involvement of calcium in transport of secretory proteins from the endoplasmic reticulum. Cell 61 (1990) 197–199.
Pinton, P., Ferrari D., Rapizzi, E., Di Virgilio, F.D., Pozzan, T. and Rizzuto, R. The Ca2+ concentration of the endoplasmic reticulum is a key determinant of ceramide-induced apoptosis: significance for the molecular mechanism of Bcl-2 action. EMBO J. 20 (2001) 2690–2701.
Tagliarino, C., Pink, J.J., Dubyak, G.R., Nieminen, A.L. and Boothman, D.A. Calcium is a key signaling moleculae in β-lapachone-mediated cell death. J. Biol. Chem. 276 (2001) 19150–19159.
Jayadev, S., Barrett, J.C. and Murphy, E. Elevated ceramide is downstream of altered calcium homeostasis in low serum-induced apoptosis. AJP-Cell Physiol. 279 (2000) 1640–1647.
Nakamura, K., Bossy-Wetzel, E., Burns, K., Fadel, M.P., Lozyk, M., Goping, I.S., Opas, M. and Bleackley, R. Endoplasmic Reticulum Luminal Environment Affect Cell Sensitivity to Apoptosis. J. Cell Biol. 150 (2000) 731–740.
Zamzami, N. and Kroemer, G. Mitochondria in apoptosis. How Pandora’s box opens. Nat. Rev. Mol. Cell. Biol. 2 (2001) 67–71.
Ferri, K.F. and Kroemer, G. Mitochondria-the suicide organelles. Bioessays 23 (2001) 111–115.
Lamkanfi, M., Kalai, M and Vandenabeele. P. Caspase-12: an overview. Cell Death Differ. 11 (2004) 65–368.
Obeng, E. A. and Boise, L. H. Caspase-12 and caspase-4 are not required for caspase-dependent endoplasmic reticulum stress-induced apoptosis. J. Biol. Chem. 280 (2005) 19150–19159.
Kaufman, R. Stress signaling from the lumen of the endoplasmic reticulum Coordination of gene transcriptional and translational controls. Genes (1999) 1211–1233.
Adrain, C. and Martin, S.J. The mitochondrial apoptosome: a killer unleashed by the cytochrome seas Trends Biochem. Sci. 26 (2001) 390–397.
Nuñez, G., Benedict, M.A., Hu, Y. and Inohara, N. Caspases: the proteases of the apoptotic pathway. Oncogene 17 (1998) 3237–3245.
Equal contribution to this paper
About this article
- Apoptosis-inducing protein HAP
- Endoplasmic reticulum (ER)
- Mitochondrial membrane potential (Δωm)
- Cytochrome c