|In the biological system, most of the important cellular events, such as growth, survival, apoptosis, differentiation and migration are regulated by post-translational modifications. Aside from phosphorylation, protein methylation has emerged over the last decade as one of the major control mechanisms in protein function.|
The most well-characterized protein lysine methyltransferases (PKMT) are histone methyltransferases. They target lysine side chain of histone tails and contribute to chromatin structure and epigenetic regulation of gene expression. For many years, lysine methylation was thought to be histone- and nucleus-specific. However, increasing number of non-histone proteins, such as p53, Rubisco, cytochrome c and yeast ribosome are identified to be lysine-methylated. Moreover, our previous study revealed a potential role of Ezh2, a PKMT and polycomb group protein, in the cytosolic cell signaling of T cells.
To further substantiate the function of Ezh2 in cytosol, we chose dendritic cell as a model system, due to its large cytosolic compartment and active cytoskeletal remodeling. Our recent result indicates while Ezh2 is dispensable for the generation of dendritic cells in vitro and in vivo, Ezh2 regulates the kinetics of cell adhesion through methylation of a cytoskeletal protein. Further characterization of this and other lysine-methylated proteins is a work in progress.
Protein sequence analysis also suggested that many uncharacterized SET-domain containing proteins are involved in lysine methylation. To determine functional significance of PKMT in the cytosol, we selected and characterized novel SET-domain proteins, which are localized predominately in the cytosol and play a potential functional role in lymphocytes. Given the substantial evidence showing the involvement of lysine methylation in cellular functions, the study of novel protein lysine methyltransferases is a promising research topic.
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