HMG-I/Y, a new c-Myc target gene and potential oncogene

Lisa Wood, Mita Mukherjee, Christine E. Dolde, Yi Xu, Joseph F. Maher, Tracie E. Bunton, John B. Williams, Linda M S Resar

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)5490-5502
Number of pages13
JournalMolecular and Cellular Biology
Volume20
Issue number15
DOIs
StatePublished - Aug 2000
Externally publishedYes

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HMGA1a Protein
myc Genes
Oncogenes
Proto-Oncogene Proteins c-myc
High Mobility Group Proteins
Burkitt Lymphoma
Fibroblasts
Estradiol Receptors
Cell Line
Neoplasms
Protein Synthesis Inhibitors
Oncogene Proteins
Cycloheximide
Nude Mice
Mutagenesis
Genes
Chromatin
Transfection
Carrier Proteins
Proteins

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Wood, L., Mukherjee, M., Dolde, C. E., Xu, Y., Maher, J. F., Bunton, T. E., ... Resar, L. M. S. (2000). HMG-I/Y, a new c-Myc target gene and potential oncogene. Molecular and Cellular Biology, 20(15), 5490-5502. https://doi.org/10.1128/MCB.20.15.5490-5502.2000

HMG-I/Y, a new c-Myc target gene and potential oncogene. / Wood, Lisa; Mukherjee, Mita; Dolde, Christine E.; Xu, Yi; Maher, Joseph F.; Bunton, Tracie E.; Williams, John B.; Resar, Linda M S.

In: Molecular and Cellular Biology, Vol. 20, No. 15, 08.2000, p. 5490-5502.

Research output: Contribution to journalArticle

Wood, L, Mukherjee, M, Dolde, CE, Xu, Y, Maher, JF, Bunton, TE, Williams, JB & Resar, LMS 2000, 'HMG-I/Y, a new c-Myc target gene and potential oncogene', Molecular and Cellular Biology, vol. 20, no. 15, pp. 5490-5502. https://doi.org/10.1128/MCB.20.15.5490-5502.2000
Wood L, Mukherjee M, Dolde CE, Xu Y, Maher JF, Bunton TE et al. HMG-I/Y, a new c-Myc target gene and potential oncogene. Molecular and Cellular Biology. 2000 Aug;20(15):5490-5502. https://doi.org/10.1128/MCB.20.15.5490-5502.2000
Wood, Lisa ; Mukherjee, Mita ; Dolde, Christine E. ; Xu, Yi ; Maher, Joseph F. ; Bunton, Tracie E. ; Williams, John B. ; Resar, Linda M S. / HMG-I/Y, a new c-Myc target gene and potential oncogene. In: Molecular and Cellular Biology. 2000 ; Vol. 20, No. 15. pp. 5490-5502.
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