Human protein lysine methyltransferases

Figure 2 Selected human protein lysine methyltransferases and their target sites on histones [11].

Protein lysine methyltransferases (PKMTs) are a family of enzymes that transfer the activated methyl group from S-adenosyl-L-methionine (SAM) to specific lysine residues on various substrates. The PKMTs have been causally linked to various human diseases including cancer [140], Huntington s disease [141], and growth defects [142, 143]. The substrates of the PKMTs are typically histones [144-146], but there are several methyltransferases methylate non-histone substrates, such as the tumor suppressor p53 [147, 148], the estrogen receptor ERa [149], and the ATPase Reptin [150]. Given the importance of these enzymes in normal and... 

There is a school of thought, which believes that HMTases are tumor suppressors especially the lysine methyltransferases because of the loss of SET domain proteins in tumor conditions, exceptions do exist like Ezh2. The well-known example of the above is RIZl, which interacts with Rb protein (again the same tumor suppressor). RIZ-1 is in chromosome lp36 region, which is commonly deleted, in more than a dozen different types of human cancers. Riz-1 expression is commonly silenced in many tumors including breast cancer, liver cancer, colon cancer, neuroblastoma, melanoma, lung cancer and osteosarcoma (Kim et al, 2003). 

In humans, carnitine is either obtained from the diet or synthesised de novo (Fig. 1). Carnitine biosynthesis in higher eukaryotes starts when protein-bound L-lysine is trimethylated by a protein-dependent methyltransferase to form e-N-trimethyllysine. Upon degradation of these proteins, free e-N-trimethyllysine becomes available and is... 

In humans, camitine is either obtained from the diet or synthesised de novo (Fig. 1). Camitine biosynthesis in higher eukaryotes starts when protein-bound L-lysine is trimethylated by a protein-dependent methyltransferase to form e-N-trimethyllysine. Upon degradation of these proteins, free e-N-trimethyllysine becomes available and is hydroxylated at the 3-position by e-N-trimethyllysine hydroxylase. Subsequently, P-hydroxy- e-N-trimethyllysine is cleaved into ytrimethylaminobutyraldehyde and glycine by p-hydroxy-e-N-trimethyllysine aldolase, after which the aldehyde is oxidized by y-trimethylaminobutyraldehyde dehydrogenase to yield y-butyrobetaine. Finally, y-buty-robetaine is hydroxylated at the 3-position by "j utyrobetaine hydroxylase (y BBH) to produce L-camitine (see Fig. 1). 

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