Fundamental Research Division
The DRF at the CEA assemble approximately 6,000 scientists since January 2016.
After 40 years of research, BIG researchers and their partners have uncovered the cause of tubulin detyrosination. The surprise: it is not one enzyme, but two that are capable of modifying this essential component of the cell skeleton.
Microtubules are dynamic fibers present in all cells. Formed by the assembly of two proteins (α-tubulin and β-tubulin), microtubules handle many functions, such as participating in cell migration or separating the chromosomes intended for the two daughter cells during cell division. These functions are regulated by the existence of "signals" present on the surface of microtubules. These signals are biochemical modifications of amino acids, carried out by several enzymes that modify the tubulins.
The activity of one of these enzymes was first demonstrated in 1977 by Argentine researchers who named it TCP (tubulin carboxypeptidase). This enzyme, which until now had never been identified (its size and sequence remained unknown), functions to remove the last amino acid, a tyrosine, from the tip of the α-tubulin, in a reaction known as detyrosination. A reverse enzyme, TTL ligase, is responsible for repositioning the tyrosine in its place, also known as tyrosination. This cycle of detyrosination/tyrosination is vital for the cell and the organism. For instance, massive (abnormal) detyrosination is observed in a number of severe cancers as well as heart conditions.
In the end, not one, but two enzymes were discovered! Scientists already knew about these enzymes, named VASH1 and VASH2, but did not know that they were associated with the cytoskeleton.
Scientists hope, by improving the knowledge of this detyrosination/tyrosination cycle and by not modulating it, that they will be able to improve the fight against certain cancers as well as make progress in our understanding of brain and cardiac functions.
This result was the subject of a press release.
Vasohibins/SVBP are tubulin carboxypeptidases
(TCP) that regulate neuron differentiation | Science
CEA is a French government-funded technological research organisation in four main areas: low-carbon energies, defense and security, information technologies and health technologies. A prominent player in the European Research Area, it is involved in setting up collaborative projects with many partners around the world.