Alternatively spliced mdm2 transcripts with loss of p53 binding domain sequences: transforming ability and frequent detection in human cancer.
Nat Med
; 2(8): 912-7, 1996 Aug.
Article
em En
| MEDLINE
| ID: mdl-8705862
ABSTRACT
The mdm2 oncogene encodes a 90-kilodalton nuclear phosphoprotein that binds and inactivates the p53 tumor suppressor protein. Here we report the observation of five alternatively spliced mdm2 gene transcripts in a range of human cancers and their absence in normal tissues. Transfection of NIH 3T3 cells with each of these forms gave foci of morphologically transformed cells. A higher frequency of splice variants lacking p53 binding domain sequences was found in late-stage and high-grade ovarian and bladder carcinomas. Four of the splice variants show loss of p53 binding, consistent with partial deletion of sequences encoding the p53 binding domain, but retain carboxyterminal zinc-finger domains. These observations suggest a reassessment of the transforming mechanisms of mdm2 and its relation to p53.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Nucleares
/
Proteína Supressora de Tumor p53
/
Proteínas Proto-Oncogênicas
/
Processamento Alternativo
/
Proteínas de Neoplasias
Tipo de estudo:
Diagnostic_studies
Limite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Nat Med
Assunto da revista:
BIOLOGIA MOLECULAR
/
MEDICINA
Ano de publicação:
1996
Tipo de documento:
Article
País de afiliação:
Reino Unido