Modulación de la actividad y especificidad enzimáticas a través de modificaciones postraduccionales (PTM)...

Post-translational modifications (PTM) (including, but not limited to, acetylation, methylation, ubiquitylation, SUMOylation and phosphorylation) offer one of the key regulatory mechanisms available to the cell. Histone PTMs catalyzed by histone modifying enzymes are perhaps the most studied PTMs in the last two decades and are known to play a critical role in regulation of gene expression. There is extensive crosstalk among different PTMs that affects activity and specificity of histone modifying enzymes, but deciphering mechanism and process by which PTMs are written and modified has proved to be challenging without understanding key underlying principles. Therefore, exploration of how PTMs are written under influence of existing PTMs (e.g., on histone) as well as general mechanisms governing their crosstalk are of fundamental importance. In this review article, we examine and analyze some previous results which show that pre-installed PTMs on substrates (e.g., modified peptides or nucleosomes) can stimulate the activity and change the specificity of histone modifying enzymes for installing new PTMs. We term such stimulation effects as PTM-induced substrate-assisted stimulations (PTM-induced SAS) and discuss some possible origin of such stimulations in certain cases. Possible role of water molecules in PTM crosstalk in the nucleosome context is also discussed. Although the focus of this review article is mainly on some of the crosstalk involving histone methylation stimulated by pre-installed methylation, acetylation or ubiquitylation, the PTM-induced SAS also exists in some other PTM crosstalk, and PTM-induced inhibition can be present as well. PTM-induced stimulations or inhibitions of enzyme activity may provide a unique way and attractive mechanism for regulation and signaling, but detailed studies are still necessary to fully understand how the stimulations/inhibitions are created and translated into altered activities and specificity for histone modifying enzymes or some other systems.