Biological processes and signal transduction pathways regulated by the protein methyltransferase SETD7 and their significance in cancer

Abstract

Protein methyltransferases have been shown to methylate histone and non-histone proteins, leading to regulation of several biological processes that control cell homeostasis. Over the past few years, the histone-lysine N-methyltransferase SETD7 (SETD7; also known as SET7/9, KIAA1717, KMT7, SET7, SET9) has emerged as an important regulator of at least 30 non-histone proteins and a potential target for the treatment of several human diseases. This review discusses current knowledge of the structure and subcellular localization of SETD7, as well as its function as a histone and non-histone methyltransferase. This work also underlines the putative contribution of SETD7 to the regulation of gene expression, control of cell proliferation, differentiation and endoplasmic reticulum stress, which indicate that SETD7 is a candidate for novel targeted therapies with the aim of either stimulating or inhibiting its activity, depending on the cell signaling context.

Cancer therapeutics: a context-dependent target

The involvement of the methyltransferase SETD7 in cell proliferation, differentiation and endoplasmic reticulum (ER) stress makes it a promising therapeutic target for cancer. By transferring methyl groups to lysine residues on DNA packaging proteins, histones, as well as on over 30 non-histone proteins, SETD7 regulates gene expression and influences protein function and stability. Inês de Albuquerque Almeida Batista and Luisa A. Helguero at the University of Aveiro, Portugal, review the latest knowledge on SETD7 activity highlighting its tissue-specific effects on cell differentiation and proliferation and its ability to promote the transcription of genes that mitigate ER stress. Further understanding SETD7’s effects in disease conditions will help determine whether stimulating or inhibiting SETD7 activity in particular cell signaling contexts represents an effective approach for the treatment of cancer.