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HMG-I/Y, a new c-Myc target gene and potential oncogene.
Wood, L J; Mukherjee, M; Dolde, C E; Xu, Y; Maher, J F; Bunton, T E; Williams, J B; Resar, L M.
Afiliação
  • Wood LJ; Hematology Division, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Mol Cell Biol ; 20(15): 5490-502, 2000 Aug.
Article em En | MEDLINE | ID: mdl-10891489
ABSTRACT
The HMG-I/Y gene encodes the HMG-I and HMG-Y proteins, which function as architectural chromatin binding proteins important in the transcriptional regulation of several genes. Although increased expression of the HMG-I/Y proteins is associated with cellular proliferation, neoplastic transformation, and several human cancers, the role of these proteins in the pathogenesis of malignancy remains unclear. To better understand the role of these proteins in cell growth and transformation, we have been studying the regulation and function of HMG-I/Y. The HMG-I/Y promoter was cloned, sequenced, and subjected to mutagenesis analysis. A c-Myc-Max consensus DNA binding site was identified as an element important in the serum stimulation of HMG-I/Y. The oncoprotein c-Myc and its protein partner Max bind to this site in vitro and activate transcription in transfection experiments. HMG-I/Y expression is stimulated by c-Myc in a Myc-estradiol receptor cell line in the presence of the protein synthesis inhibitor cycloheximide, indicating that HMG-I/Y is a direct c-Myc target gene. HMG-I/Y induction is decreased in Myc-deficient fibroblasts. HMG-I/Y protein expression is also increased in Burkitt's lymphoma cell lines, which are known to have increased c-Myc protein. Like Myc, increased expression of HMG-I protein leads to the neoplastic transformation of both Rat 1a fibroblasts and CB33 cells. In addition, Rat 1a cells overexpressing HMG-I protein form tumors in nude mice. Decreasing HMG-I/Y proteins using an antisense construct abrogates transformation in Burkitt's lymphoma cells. These findings indicate that HMG-I/Y is a c-Myc target gene involved in neoplastic transformation and a member of a new class of potential oncogenes.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fatores de Transcrição / Proteínas de Grupo de Alta Mobilidade / Proteínas Proto-Oncogênicas c-myc / Proteínas de Neoplasias Tipo de estudo: Prognostic_studies Idioma: En Revista: Mol Cell Biol Ano de publicação: 2000 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fatores de Transcrição / Proteínas de Grupo de Alta Mobilidade / Proteínas Proto-Oncogênicas c-myc / Proteínas de Neoplasias Tipo de estudo: Prognostic_studies Idioma: En Revista: Mol Cell Biol Ano de publicação: 2000 Tipo de documento: Article País de afiliação: Estados Unidos
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