It causes the production of a protein which, as a transcription factor, controls the expression of up to 15 % of all human genes. When this gene mutates to an oncogene, the cell proliferates excessively and apoptosis is inhibited. Thereby the gene plays a decisive role in the development of many tumors.

The problem is that pharmacological substances do not target Myc as it does not have enzymatic activity of its own. Thus, scientists worldwide are trying to find alternative ways to inhibit this oncogene. A team of scientists led by Klaus Bister and Markus Hartl of the Institute of Biochemistry and the Centre for Molecular Biosciences of the University of Innsbruck may have made an important step towards achieving this goal.

Suppressing pathological cell growth

For the first time, the scientists have shown that Myc suppresses the expression of the gene BASP1. This evidence prompted them to test the effect of BASP1 on the oncogene. In cell experiments they proved that BASP1 specifically inhibits the uncontrolled proliferation of Myc. "Until now the precise biochemical function of BASP1 is unknown", Professor Bister explains. "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." This finding may facilitate the development of new drugs which keep the development of tumors under control.

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Previous research has shown that when embryonic stem cells lack Ezh2, genes for many cell differentiation pathways, not just the skin, lose their "molecular clamps" and become activated. In skin stem cells, however, these genes also lose these molecular clamps, but only the skin differentiation genes become activated. In examining why only the skin pathway is switched on when the clamp is missing, the researchers found that AP1, the transcription factor that selectively activates skin differentiation genes, is present in both basal and differentiating skin cells. Without Ezh2, AP1 could bind and start to activate these genes in the basal layer, before the genes are normally expressed.

Another difference is that in embryonic stem cells, as soon as the molecular clamp is removed from muscle and neuronal genes, for example, an "activating mark" helps to switch on genes. In the skin stem cells this mark is not present on the non-skin genes, helping to keep them silent.

"Embryonic stem cells must be flexible -- they produce all the cells of the animal," explains Fuchs. "As development proceeds, the resident progenitors of developing tissues become increasingly more restricted in their repertoire of differentiation programs. As the embryo develops, tissue-specific stem cells seem to remove the activating mark on those programs that will never be used, thereby switching off the wrong programs permanently. Then, to activate the right programs, the genes become dependent upon tissue-specific transcription factors."

"The system is clearly more complicated than this," Fuchs adds, "but the result is a series of intrinsic and extrinsic factors that control gene expression."

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