Transcription Factor ATF2 Regulation by the JNK Signal Transduction Pathway

作者：Shashi Kumar Gupta, Debra Campbell, Benoît Dérijard, Roger J. Davis · 发表于：Science · 年份：1995 · DOI：10.1126/science.7824938 · 被引用次数：1455 · 研究领域：CRISPR and Genetic Engineering、interferon and immune responses、NF-κB Signaling Pathways

Treatment of cells with pro-inflammatory cytokines or ultraviolet radiation causes activation of the c-Jun NH2-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 NH2-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.