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Beschreibung

N-lysine methyltransferase SETD6 (UniProt: Q8TBK2, also known as SET domain-containing protein 6) is encoded by the SETD6 gene (Gene ID: 79918) in human. N-lysine methyltransferase SETD6 is a SET domain protein that specifically monomethylates lysine 310 of NF-kappa B-p65 that leads to down-regulation of NF-kappa B transcription factor activity. It can also monomethylate lysine 8 of H2AZ (H2AZK8me1). SETD6 is required for the maintenance of embryonic stem cell self-renewal. Primary urothelial cells and normal bladder tissue have almost undetectable SETD6 levels that are shown to increase in transformed urothelial cells and is further increased in bladder cancer cells and tissues. Overexpression of SETD6 in transformed urothelial cells increases their survival and colony formation. SETD6 is shown to interact with the oxidative stress sensor protein DJ1, which is required for Nrf2-dependent transcription of antioxidant target genes. Under basal conditions, SETD6 and DJ1 are associated at chromatin and SETD6 inhibits DJ1 activity, which leads to the repression of Nrf2-dependent transcription. However, under conditions of oxidative stress SETD6 mRNA and protein levels decline that leads to elevation in Nrf2 expression and diminish interaction between SETD6 and DJ1. Two isoforms of SETD6 have been described that are produced by alternative splicing. (Ref.: Mukherjee, N., et al. (2017). Oncotarget. 8(9), 15114-15125, Chen, A., et al. (2016). Biochim. Biophys. Acta. 1859(2):420-427).