Tuesday, 02 April 2019 11:56

Würzburg: New insights into growth factors in vitro Featured

Using cell cultures scientists from the University of Würzburg led by Prof. Elmar Wolf have discovered a new mechanism how genes are transcribed in tumor cells. A protein named Myc playes a key role in this process. The researchers were able to show how oncogenic concentrations of the protein Myc allow an uncontrolled cell growth.


Myc is a normal protein which, however, through a mutation, can promote the formation of tumours (oncogene). It binds to the promoter area of all genes where the transcription of the DNA is triggered. So far, the exact mode of action of the protein has been poorly understood. Using mass spectrometric investigations, the scientists were able to show that Myc controls the composition of the polymerase II with the aid of a small set of transcriptional extension factors.

The protein Myc improves the function and quality of RNA polymerase II by enabling it to perform its function of connecting individual nucleotides into a long nucleotide chain without interruption and in the right direction on the DNA strand. Thereby, Myc maintains the high extension rate.

A subunit of the extension factor DSIF, called SPT5, is involved. Myc binds to this subunit, makes it available to promoters and enables a enzyme-dependent transfer of this subunit to theRNA polymerase II.

In tumors, the protein Myc is expressed in remarkably high amounts. By sequestering the SPT5 subunit in non-functional complexes, the expression of growth suppressing genes is reduced. This allows the cell to divide uncontrollably.

The findings are of interest for further cancer research. The authors hope that a better understanding of the mode of action of transcription factors also shows ways in which these can be inhibited in malignant diseases.

The researchers presented their results in the journal Molecular Cell:
Baluapuri, A., Hofstetter, J., Dudvarski Stankovic, N., Endres, T., Bhandare, P., Vos, S.M., Adhikari, B., Black, J.D., Narain, A., Vogt, M., Wang, S.-Y., Dark, R., Jung, L.A., Vanselow, J.T., Wiegering, A., Geyer, M., Maric, H.M., Gallant, P., Walz, S., Schlosser, A., Cramer, P., Eilers, M. & Wolf, E. (2019). MYC recruits SPT5 to RNA polymerase II to promote processive transcription elongation. Molecular Cell 74: 1-14, 27.03.2019, DOI: 10.1016/y.molcel.2019.02.031

Source:
https://www.uni-wuerzburg.de/aktuelles/einblick/single/news/ein-protein-als-tankwart-der-krebsentstehung-1/

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