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HMG-I/Y, a new c-Myc target gene and potential oncogene.
- Source :
-
Molecular and cellular biology [Mol Cell Biol] 2000 Aug; Vol. 20 (15), pp. 5490-502. - Publication Year :
- 2000
-
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.
- Subjects :
- Animals
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
Basic-Leucine Zipper Transcription Factors
Burkitt Lymphoma
Cell Line
Cell Transformation, Neoplastic genetics
DNA-Binding Proteins genetics
DNA-Binding Proteins metabolism
Fibroblasts drug effects
Fibroblasts pathology
Gene Expression Regulation
Growth Substances genetics
Growth Substances metabolism
Growth Substances pharmacology
HMGA1a Protein
High Mobility Group Proteins immunology
High Mobility Group Proteins metabolism
Mice
Mice, Inbred BALB C
Mice, Nude
Neoplasm Proteins drug effects
Neoplasm Proteins metabolism
Promoter Regions, Genetic
Proto-Oncogene Proteins c-myc metabolism
Rats
Recombinant Proteins genetics
Recombinant Proteins metabolism
Sequence Analysis, DNA
Transcription Factors immunology
Transcription Factors metabolism
Transcription, Genetic
Tumor Cells, Cultured
High Mobility Group Proteins genetics
Neoplasm Proteins genetics
Proto-Oncogene Proteins c-myc genetics
Transcription Factors genetics
Subjects
Details
- Language :
- English
- ISSN :
- 0270-7306
- Volume :
- 20
- Issue :
- 15
- Database :
- MEDLINE
- Journal :
- Molecular and cellular biology
- Publication Type :
- Academic Journal
- Accession number :
- 10891489
- Full Text :
- https://doi.org/10.1128/MCB.20.15.5490-5502.2000