The lysine multi-switch : the impact of lysine methylation on transcription factor properties

Abstract

The amino acid lysine can undergo methylation, acylation, sumoylation or ubiquitination, making it an extremely versatile protein residue. Its involvement in the modulation of protein biological functions through de/methylation on histones has been well studied but only recently has the focus shifted towards this post-translational modification in non-histone proteins particularly transcription factors. Lysine methylation has been found to act as a switch which can directly alter function or stability, as well as indirectly alter binding affinity to target DNA motifs and protein partners. Lysine methylation has been best-studied in the tumour suppressor p53, making it the ideal transcription factor to showcase how these different mechanisms act. Other transcription factors that undergo such a post-translational modification include NFkB, STAT3 and TFIID. More recently a new family of 10 lysine methyltransferases has been described and the interaction of one of them with the ubiquitous transcription factor E4TF1-60 opens a whole new field of transcription factor control. Lysine methylation is involved in a number of diseases and has also been shown to play a role in tumorigenesis. Targetting specificly modified over-active transcription factors is a potential form of anti-cancer therapy although it is a very delicate process, which still requires extensive research.