Posttranslational sumoylation

The transcriptional activity of NRs is also modulated by various posttranslational modifications of the receptors themselves or of their coregulatory proteins. Phosphorylation, as well as several other types of modification, such as acetylation, SUMOylation, ubiquitinylation, and methylation, has been reported to modulate the functions of NRs, potentially constituting an important cellular integration mechanism. In addition to the modifications of the receptors themselves, such modifications have been reported for their coactivators and corepressors. Therefore, these different modes of regulation reveal an unexpected complexity of the dynamics of NR-mediated transcription. 

Small Ubiquitin-like modifier (SUMO) is a conserved protein that is ubiquitously expressed in eukaryotes and is essential for viability. It serves as a reversible posttranslational modifier by forming an isopeptide bond with lysine residues in many target proteins, in a catalytic process termed SUMOylation. SUMOylation of proteins results in altered inter- or intramolecular interactions of the modified target (Fig. 1). 

A high proportion of the positiveiy charged basic amino acids lysine and arginine within these flexible tails are frequent targets for extensive posttranslational modifications (Berger, 2002). Such modifications include the acetylation of lysine residues, the methylation of lysine and arginine residues, the ubiquitination of lysine residues, the phosphorylation of serine and threonine residues, the sumoylation of lysine residues, and the poly ADP-ribosylation of glutamic acid residues. 

The N-terminal tails of histone proteins are rich in arginine and lysine residues and undergo various types of posttranslational modifications. There are small modifications such as acetylation, methylation, phosphorylation but also the attachment of larger peptide groups such as ubiquitinylation and sumoylation [1]. This has an impact on chromatin structure and subsequently on gene transcription and the epigenetic maintenance of altered transcription after cell division [2],... 

From ligand sensitization to translation of genes, every single process in cells is dependent on the intracellular levels and activity of various signaling molecules and pathways. These signaling events lead to very critical posttranslational modifications such as phosphorylation, sumoylation, ubiquitination and others that are... 

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