Potential Inhibitor of the Myc Oncogene Identified

Researchers seeking to understand the molecular factors that cause normal cells to become cancerous have found that transformation induced by the activity of the Myc oncogene can be inhibited by the action of a potential tumor suppressor gene called brain acid-soluble protein 1 (BASP1).

Myc is a very strong proto-oncogene, and it is very often found to be upregulated in many types of cancers. The Myc protein encoded by this gene is a transcription factor that activates expression of a great number of genes through binding on consensus sequences (Enhancer Box sequences (E-boxes)) and recruiting histone acetyltransferases (HATs). It can also act as a transcriptional repressor. By binding Miz-1 transcription factor and displacing the p300 coactivator, it inhibits expression of Miz-1 target genes. Myc is activated upon various mitogenic signals such as Wnt, Shh, and EGF (via the MAPK/ERK pathway). By modifying the expression of its target genes, Myc activation results in numerous biological effects.

Investigators at University of Innsbruck (Austria) studied the relationship of Myc to BASP1 in cell cultures. They reported in the March 18, 2009, online edition of the journal the Proceedings of the [U.S.] National Academy of Sciences (PNAS) that BASP1 mRNA and protein expression was specifically suppressed in fibroblasts transformed by the v-Myc oncogene, but not in cells transformed by other oncogenic agents. Downregulation of the BASP1 gene was a necessary event in Myc-induced oncogenesis and defined the BASP1 protein as a potential tumor suppressor.

"Until now the precise biochemical function of BASP1 was unknown,” said senior author Dr. Klaus Bister, professor of biochemistry at the University of Innsbruck. "However, in our experiments we have found clear evidence that Myc-induced cell transformation can be specifically inhibited by BASP1, and consequently, the gene functions as a tumor suppressor.”

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University of Innsbruck