Open AccessHMG-I/Y, a New c-Myc Target Gene and Potential Oncogene
Author(s) -
Lisa J. Wood,
Mita Mukherjee,
Christine Dolde,
Yi Xu,
Joseph F. Maher,
Tracie E. Bunton,
John Williams,
Linda Resar
Publication year - 2000
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.20.15.5490-5502.2000
Subject(s) - biology , microbiology and biotechnology , oncogene , hmg coa reductase , transfection , dna binding protein , neoplastic transformation , retinoblastoma like protein 1 , gene expression , transcription factor , gene , cancer research , carcinogenesis , cell cycle , biochemistry , reductase , enzyme
TheHMG-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 ofHMG-I/Y . TheHMG-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 ofHMG-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 thatHMG-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 thatHMG-I/Y is a c-Myc target gene involved in neoplastic transformation and a member of a new class of potential oncogenes.