Transcription Factor ATF2 Regulation by the JNK Signal Transduction Pathway

TLDR

JNK is activated in cells by pro‑inflammatory cytokines or ultraviolet radiation. JNK phosphorylates ATF2 on two threonine residues, and mutating these sites or inhibiting JNK diminishes ATF2 transcriptional activity and downstream gene expression, showing that JNK regulates ATF2‑mediated transcription.

Abstract

Treatment of cells with pro-inflammatory cytokines or ultraviolet radiation causes activation of the c-Jun NH 2 -terminal protein kinase (JNK). Activating transcription factor-2 (ATF2) was found to be a target of the JNK signal transduction pathway. ATF2 was phosphorylated by JNK on two closely spaced threonine residues within the NH 2 -terminal activation domain. The replacement of these phosphorylation sites with alanine inhibited the transcriptional activity of ATF2. These mutations also inhibited ATF2-stimulated gene expression mediated by the retinoblastoma (Rb) tumor suppressor and the adenovirus early region 1A (E1A) oncoprotein. Furthermore, expression of dominant-negative JNK inhibited ATF2 transcriptional activity. Together, these data demonstrate a role for the JNK signal transduction pathway in transcriptional responses mediated by ATF2.