DeltaNp63alpha up-regulates the Hsp70 gene in human cancer.
Cancer Res
; 65(3): 758-66, 2005 Feb 01.
Article
em En
| MEDLINE
| ID: mdl-15705872
ABSTRACT
HSP70, a stress response protein, is known to be a determinant of cell death and cell transformation. We show that different isoforms of p63 have different transcriptional activities on hsp70 genes. DeltaNp63alpha, an abundantly expressed isoform of p63, activates (in vitro and in vivo), whereas TAp63gamma down-regulates the expression of hsp70. We further show that the transactivation domain at the NH(2) terminus of p63 represses, whereas the COOH terminus activates hsp70 transcription. In addition, DeltaNp63alpha regulates transcription of the hsp70 gene through its interaction with the CCAAT binding factor and NF-Y transcription factors which are known to form a complex with the CCAAT box located in the hsp70 promoter. Moreover, DeltaNp63alpha expression correlates with HSP70 expression in all head and neck cancer cell lines. Finally, we show colocalization of DeltaNp63alpha and HSP70 in the epithelium and coexpression of both proteins in 41 primary head and neck cancers. Our study provides strong evidence for the physiologic association between DeltaNp63alpha and hsp70 in human cancer, thus further supporting the oncogenic potential of DeltaNp63alpha.
Buscar no Google
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fosfoproteínas
/
Transativadores
/
Proteínas de Choque Térmico HSP70
/
Neoplasias
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Cancer Res
Ano de publicação:
2005
Tipo de documento:
Article
País de afiliação:
Estados Unidos