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Journal article
Elk-1 associates with the mitochondrial permeability transition pore complex in neurons
Proceedings of the National Academy of Sciences - PNAS, v 103(13), pp 5155-5160
28 Mar 2006
PMID: 16549787
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The nuclear transcription factor E-26-like protein 1 (Elk-1) is thought to impact neuronal differentiation [Sharrocks, A. D. (2001)
Nat. Rev. Mol. Cell Biol.
2, 827–837], cell proliferation [Sharrocks, A. D. (2002)
Biochem. Soc. Trans.
30, 1–9], tumorigenesis [Chai, Y. L., Chipitsyna, G., Cui, J., Liao, B., Liu, S., Aysola, K., Yezdani, M., Reddy, E. S. P. & Rao, V. N. (2001)
Oncogene
20, 1357–1367], and apoptosis [Shao, N., Chai, Y., Cui, J., Wang, N., Aysola, K., Reddy, E. S. P. & Rao, V. N. (1998)
Oncogene
17, 527–532]. In addition to its nuclear localization, Elk-1 is found throughout the cytoplasm, including localization in neuronal dendrites [Sgambato, V., Vanhoutte, P., Pages, C., Rogard, M., Hipskind, R., Besson, M. J. & Caboche, J. (1998)
J. Neurosci.
18, 214–226], raising the possibility that Elk-1 may have alternative extranuclear functions in neurons. Using coimmunoprecipitation and reciprocal coimmunoprecipitation from adult rat brain, we found an association between Elk-1 protein and the mitochondrial permeability transition pore complex (PTP), a structure involved in both apoptotic and necrotic cell death. Electron microscopy in adult rat brain sections confirmed this association with mitochondria. Elk-1 was also identified from purified mitochondrial fractions by using Western blotting, and Elk-1 increased its association with mitochondria following proapoptotic stimuli. Consistent with a role for Elk-1 in neuron viability, overexpression of Elk-1 in primary neurons decreased cell viability, whereas Elk-1 siRNA-mediated knockdown increased cell viability. This decrease in viability induced by Elk-1 overexpression was blocked with application of a PTP inhibitor. These results show an association of the nuclear transcription factor Elk-1 with the mitochondrial PTP and suggest an additional extranuclear function for Elk-1 in neurons.
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Details
- Title
- Elk-1 associates with the mitochondrial permeability transition pore complex in neurons
- Creators
- L. E. Barrett - Departments of Neuroscience andE. J. Van Bockstaele - Thomas Jefferson UniversityJ. Y. Sul - Departments of Neuroscience andH. Takano - Departments of Neuroscience andP. G. Haydon - Departments of Neuroscience andJ. H. Eberwine - University of Pennsylvania
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, v 103(13), pp 5155-5160
- Publisher
- National Academy of Sciences
- Number of pages
- 6
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000236472500065
- Scopus ID
- 2-s2.0-33645527571
- Other Identifier
- 991021903300604721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology