The transcription factor TCF/Elk-1: A nuclear sensor of changes in the cellular redox status

Abstract

The ternary complex factor (TCF) and the serum response factor (SRF) are nuclear transcription factors which are essential for efficient signal transduction via the serum response clement SRE in the c-fos promoter. Their activation leads to a rapid induction of c-fos gene expression. Activation of mitogen-activated protein kinases (MAPK) by signalling cascades and subsequent TCF phosphorylation are known to be essential steps in this transcriptional activation. In transient transfections we could show activation of a SRE dependent promoter following treatment of HeLa cells with either the oxidant H2O2 or various antioxidants. This activation is dependent on the presence of both an intact SRE as well as a TCF binding site. In gel shifts we observed changes in the migration of ternary complexes which were due to hyperphosphorylation of TCF/Elk-1. In-gel kinase assays showed an activation of MAPK Ser/Thr kinase activity by both oxidant and antioxidant stimuli, which temporally correlates with the appearance of hyperphosphorylated TCF/Elk-1. Thus antagonistic intracellular redox changes can lead to the same functional modulation of the nuclear transcription factor TCF/Elk-1 that was previously described following mitogenic stimuli.