Oncogene jun encodes a sequence-specific trans- activator similar to AP-1

Abstract

Proto-oncogenes encode proteins with three main sites of action: the cell-surface membrane, the cytoplasm and the nucleus. Although the exact biochemical function of most proto-oncogene products is not understood, several of them are known to be involved in signal transduction. A role in gene regulation through DNA binding has been suggested for a recently isolated member of the group of oncogenes acting at the nucleus, v-jun. The C-terminus of the putative v-jun-encoded protein is similar in sequence to the C-terminus of the yeast transcriptional activator GCN4 (refs 8, 9), which forms its minimal DNA-binding domain. GCN4 binds to specific sites whose consensus sequence is highly similar to the recognition sequence of the mammalian transcriptional activator AP-1 (refs 12, 13). Like GCN4, AP-1 binds to promoter elements of specific genes and activates their transcription. Because of the similarity between the recognition sites for GCN4 and AP-1, we examined the possibility that AP-1 could be the product of the c-jun proto-oncogene. The experimental results reported here indicate that the JUN oncoprotein is a sequence-specific transcriptional activator similar to AP-1.

c-Jun, at the crossroad of the signaling network

“…GCN4 and the mammalian AP-1, known at that time only as a transcription factor interacting with a specific enhancer sequence, share the same DNA binding specificity (Short, 1987;Haluska et al, 1988). Using this specific piece of DNA for affinity chromatography, the mammalian c-Jun was co-purified with c-Fos, marking the first identification of AP-1 as a heterodimer of c-Jun and c-Fos (Angel et al, 1988a;Harshman et al, 1988;Rauscher et al, 1988aRauscher et al, , 1988b.…”

Distinction between AP1 and NF-E2 factor-binding at specific chromatin regions in mammalian cells

“…This motif has been implicated in the regulation of a number of genes. Factors recognizing the AP1/NF-E2 motif in vivo include the well-known AP1 (homodimers of the oncogene product c-Jun, or heterodimers of c-Fos and c-Jun) (Lee et al, 1987;Angel et al, 1988b), a hematopoietic transcription factor NF-E2 (Andrews et al, 1993), the homodimers of the small maf polypeptide family, and heterodimers of the small maf with several other ubiquitous polypeptides (Blank and Andrews, 1997;Motohashi et al, 1997 and references therein).…”

Cooperation between GLI and JUN enhances transcription of JUN and selected GLI target genes

“…JUN acts primarily as activator of transcription and is regulated at different levels including activation of its own transcription thus creating a positive feedback loop (Angel et al, 1988a). Phosphorylation by JUN N-terminal kinase (JNK), a target of mitogen-activated protein kinase signaling, is crucial for full transcriptional activity of JUN (reviewed in Weston and Davis, 2007).…”