Ectopic expression of new alternative splice variant of Smac/DIABLO increases mammospheres formation
| Autor: | Gustavo U, Martinez-Ruiz, Georgina, Victoria-Acosta, Karla I, Vazquez-Santillan, Luis, Jimenez-Hernandez, Laura, Muñoz-Galindo, Gisela, Ceballos-Cancino, Vilma, Maldonado, Jorge, Melendez-Zajgla |
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| Rok vydání: | 2014 |
| Předmět: |
Proteasome Endopeptidase Complex
Transcription Genetic Gene Expression Profiling Intracellular Signaling Peptides and Proteins Breast Neoplasms Transfection Up-Regulation Gene Expression Regulation Neoplastic Mitochondrial Proteins Cytosol Spheroids Cellular Proteolysis MCF-7 Cells Humans Protein Isoforms Female Gene Regulatory Networks Original Article biological phenomena cell phenomena and immunity Apoptosis Regulatory Proteins HeLa Cells Oligonucleotide Array Sequence Analysis |
| Zdroj: | International journal of clinical and experimental pathology. 7(9) |
| ISSN: | 1936-2625 |
| Popis: | Smac-α is a mitochondrial protein that, during apoptosis, is translocated to the cytoplasm, where it negatively regulates members of the inhibitor of apoptosis (IAP) family via the IAP-binding motif (IBM) contained within its amino-terminus. Here, we describe a new alternative splice variant from Smac gene, which we have named Smac-ε. Smac-ε lacks both an IBM and a mitochondrial-targeting signal (MTS) element. Smac-ε mRNA exhibits a tissue-specific expression pattern in healthy human tissues as well as in several cancer cell lines. The steady-state levels of endogenous Smac-ε protein is regulated by the proteasomal pathway. When ectopically expressed, this isoform presents a cytosolic localization and is unable to associate with or to regulate the expression of X-linked Inhibitor of apoptosis protein, the best-studied member of IAP family. Nevertheless, over-expression of Smac-ε increases mammosphere formation. Whole genome expression analyses from these mammospheres show activation of several pro-survival and growth pathways, including Estrogen-Receptor signaling. In conclusion, our results support the functionality of this new Smac isoform. |
| Databáze: | OpenAIRE |
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