Ordinary cells shouldn't be too smart
Harvard University scientists working under the guidance of Dr. Stephen Elledge have identified several molecular "switches" that control the synthesis of proteins characteristic of the cells of the nervous system. In the development of the nervous system, these switches play an important physiological role, but outside of the nervous system, these genes are not in a depressed state for nothing. Activation of genes that stimulate the development of neurons in other cells, for example, in breast cells, allows them to exist in an unfettered state. As a result, the cells acquire the classic characteristic of malignant cells – the ability to grow in suspension.
In an earlier work, the authors showed that the REST protein, which suppresses the activity of nerve cell formation programs in most organs (mammary gland, lungs, etc.), acts as a suppressor of tumor growth. The destruction of the REST protein leads to the activation of a set of genes that give cells the characteristics of nerve progenitor cells and promotes tumor growth.
The authors suggested that a decrease in the REST protein content in cells occurs under the influence of regulatory proteins. To search for such proteins, they used the RNA interference method, measuring the REST concentration after suppressing the synthesis of each of the "suspected" proteins. The "culprit" turned out to be a well–known activator of tumor growth - beta-TRCP protein. Further investigation showed that beta-TRCP binds directly to REST and thus marks it for destruction. However, in order for this to happen, a phosphate residue must be attached to the REST molecule.
Scientists believe that by preventing the binding of beta-TRCP and REST molecules, it is possible to cure certain types of tumors whose cells express neural genetic profiles. Such gene expression profiles are characteristic of many epithelial tissues originating from the same germ leaf – ectoderm as the nervous system.
The discovery is of great value, because pharmacologists know methods of acting with the help of small molecules on enzymes that remove and attach phosphate groups to proteins.
In addition, knowing the details of the interaction between beta-TRCP and REST will help researchers working with embryonic stem cells. Differentiation of embryonic stem cells into specialized cells is very difficult to control. Therefore, blocking the interaction of beta-TRCP and REST can be a useful technique to prevent the transformation of stem cells into neurons. And accelerating the destruction of REST, on the contrary, can increase the efficiency of obtaining populations of nerve cells.
Article by Thomas F. Westbrook et al. "SCF β-TRCP controls oncogenic transformation and neural differentiation through REST degradation" is published in Nature (2008, Vol. 452:370-374).
Portal "Eternal youth" www.vechnayamolodost.ru based on materials from Harvard Medical School
25.03.2008