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High-mobility group A1 protein inhibits p53-mediated intrinsic apoptosis by interacting with Bcl-2 at mitochondria
- Source :
- Cell Death & Disease, Cell death and disease (2012)., info:cnr-pdr/source/autori:Esposito F, Tornincasa M, Federico A, Chiappetta G, Pierantoni GM, Fusco A./titolo:High-mobility group A1 protein inhibits p53-mediated intrinsic apoptosis by interacting with Bcl-2 at mitochondria./doi:/rivista:Cell death and disease/anno:2012/pagina_da:/pagina_a:/intervallo_pagine:/volume
- Publication Year :
- 2012
- Publisher :
- Nature Publishing Group, 2012.
-
Abstract
- The high-mobility group A (HMGA) proteins are a family of non-histone chromatin factors, encoded by the HMGA1 and HMGA2 genes. Several studies demonstrate that HMGA proteins have a critical role in neoplastic transformation, and their overexpression is mainly associated with a highly malignant phenotype, also representing a poor prognostic index. Even though a cytoplasmic localization of these proteins has been previously reported in some highly malignant neoplasias, a clear role for this localization has not been defined. Here, we first confirm the localization of the HMGA1 proteins in the cytoplasm of cancer cells, and then we report a novel mechanism through which HMGA1 inhibits p53-mitochondrial apoptosis by counteracting the binding of p53 to the anti-apoptotic factor Bcl-2. Indeed, we demonstrate a physical and functional interaction between HMGA1 and Bcl-2 proteins. This interaction occurs at mitochondria interfering with the ability of p53 protein to bind Bcl-2, thus counteracting p53-mediated mitochondrial apoptosis. This effect is associated with the inhibition of cytochrome c release and activation of caspases. Consistent with this mechanism, a strong correlation between HMGA1 cytoplasmic localization and a more aggressive histotype of thyroid, breast and colon carcinomas has been observed. Therefore, cytoplasmic localization of HMGA1 proteins in malignant tissues is a novel mechanism of inactivation of p53 apoptotic function.
Details
- Language :
- English
- ISSN :
- 20414889
- Volume :
- 3
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- Cell Death & Disease
- Accession number :
- edsair.doi.dedup.....7d0b9297e4d041ae3562e9dd4c1645d0