title: Ectopic expression of new alternative splice variant of Smac/DIABLO increases mammospheres formation.
abstract: 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.
authors.affiliation: Functional Cancer Genomics Laboratory, National Institute of Genomic Medicine Periférico Sur 4809, Col. Arenal Tepepan, Tlalpan 14610, Mexico.
authors.forename: Gustavo U
authors.initials: GU
authors.lastname: Martinez-Ruiz
authors.affiliation: Functional Cancer Genomics Laboratory, National Institute of Genomic Medicine Periférico Sur 4809, Col. Arenal Tepepan, Tlalpan 14610, Mexico.
authors.forename: Georgina
authors.initials: G
authors.lastname: Victoria-Acosta
authors.affiliation: Functional Cancer Genomics Laboratory, National Institute of Genomic Medicine Periférico Sur 4809, Col. Arenal Tepepan, Tlalpan 14610, Mexico.
authors.forename: Karla I
authors.initials: KI
authors.lastname: Vazquez-Santillan
authors.affiliation: Functional Cancer Genomics Laboratory, National Institute of Genomic Medicine Periférico Sur 4809, Col. Arenal Tepepan, Tlalpan 14610, Mexico.
authors.forename: Luis
authors.initials: L
authors.lastname: Jimenez-Hernandez
authors.affiliation: Functional Cancer Genomics Laboratory, National Institute of Genomic Medicine Periférico Sur 4809, Col. Arenal Tepepan, Tlalpan 14610, Mexico.
authors.forename: Laura
authors.initials: L
authors.lastname: Muñoz-Galindo
authors.affiliation: Functional Cancer Genomics Laboratory, National Institute of Genomic Medicine Periférico Sur 4809, Col. Arenal Tepepan, Tlalpan 14610, Mexico.
authors.forename: Gisela
authors.initials: G
authors.lastname: Ceballos-Cancino
authors.affiliation: Functional Cancer Genomics Laboratory, National Institute of Genomic Medicine Periférico Sur 4809, Col. Arenal Tepepan, Tlalpan 14610, Mexico.
authors.forename: Vilma
authors.initials: V
authors.lastname: Maldonado
authors.affiliation: Functional Cancer Genomics Laboratory, National Institute of Genomic Medicine Periférico Sur 4809, Col. Arenal Tepepan, Tlalpan 14610, Mexico.
authors.forename: Jorge
authors.initials: J
authors.lastname: Melendez-Zajgla
mesh_terms: D051017:Apoptosis Regulatory Proteins; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D003600:Cytosol / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D061986:MCF-7 Cells; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D020033:Protein Isoforms; D059748:Proteolysis; D018874:Spheroids, Cellular; D014158:Transcription, Genetic; D014162:Transfection; D015854:Up-Regulation
chemical_list: D051017:Apoptosis Regulatory Proteins; C412403:DIABLO protein, human; D047908:Intracellular Signaling Peptides and Proteins; D024101:Mitochondrial Proteins; D020033:Protein Isoforms; D046988:Proteasome Endopeptidase Complex
keywords: Smac-ε; breast; cancer; tumorigenicity