High-mobility group A1 protein inhibits p53-mediated intrinsic apoptosis by interacting with Bcl-2 at mitochondria. (Articolo in rivista)

Type

• Articolo in rivista (Classe)
• Prodotto della ricerca (Classe)

Label

• High-mobility group A1 protein inhibits p53-mediated intrinsic apoptosis by interacting with Bcl-2 at mitochondria. (Articolo in rivista) (literal)

Anno

• 2012-01-01T00:00:00+01:00 (literal)

Alternative label

• Esposito F, Tornincasa M, Federico A, Chiappetta G, Pierantoni GM, Fusco A. (2012)
  High-mobility group A1 protein inhibits p53-mediated intrinsic apoptosis by interacting with Bcl-2 at mitochondria.
  in Cell death and disease
  (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori

• Esposito F, Tornincasa M, Federico A, Chiappetta G, Pierantoni GM, Fusco A. (literal)

Rivista

• Cell death and disease (Rivista)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni

• Istituto di Endocrinologia ed Oncologia Sperimentale del CNR c/o Dipartimento di Biologia e Patologia Cellulare e Molecolare, Facoltà di Medicina e Chirurgia di Napoli, Università degli Studi di Napoli Federico II, Naples, Italy. (literal)

Titolo

• High-mobility group A1 protein inhibits p53-mediated intrinsic apoptosis by interacting with Bcl-2 at mitochondria. (literal)

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. (literal)

Prodotto di

• Istituto per l'endocrinologia e l'oncologia \"Gaetano Salvatore\" (IEOS) (Istituto)
• Ruolo delle proteine cromatiniche nella tumorigenesi (SV.P15.001.002) (Modulo)

Autore CNR

• ALFREDO FUSCO (Unità di personale interno)
• Mara Tornincasa (Unità di personale esterno)
• Antonella Federico (Persona)
• Francesco Esposito (Persona)
• GIOVANNA MARIA PIERANTONI (Persona)

Incoming links:

Autore CNR di

• ALFREDO FUSCO (Unità di personale interno)
• Antonella Federico (Persona)
• GIOVANNA MARIA PIERANTONI (Persona)
• Francesco Esposito (Persona)
• Mara Tornincasa (Unità di personale esterno)

Prodotto

• Istituto per l'endocrinologia e l'oncologia \"Gaetano Salvatore\" (IEOS) (Istituto)
• Ruolo delle proteine cromatiniche nella tumorigenesi (SV.P15.001.002) (Modulo)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#rivistaDi

• Cell death and disease (Rivista)