COP9 signalosome-directed c-Jun activation/stabilization is independent ofJNK

The basic region-leucine zipper transcription factor c-Jun regulates gene e xpression and cell function. It participates in the formation of homo- or h eterodimeric complexes that specifically bind to DNA sequences called activ ating protein 1 (AP-1) sites, The stability and activity of c-Jun is regula ted by phosphorylation within the N-terminal activation domain. Mitogen- an d stress-activated c-Jun N-terminal kinases (JNKs) were previously the only described enzymes phosphorylating c-Jun at the N terminus in vivo. In this report we demonstrate a JNK-independent activation of c-Jun in vivo direct ed by the constitutive photomorphogenesis (COP9) signalosome. The overexpre ssion of signalosome subunit 2 (Sgn2), a subunit of the COP9 signalosome, l eads to de novo assembly of the complex with a partial incorporation of the overexpressed subunit, The de novo formation of COP9 signalosome parallels an increase of c-Jun protein resulting in elevated AP-1 transcriptional ac tivity. The c-Jun activation caused by Sgn2 overexpression is independent o f JNK and mitogen-activated protein kinase kinase 4. The data demonstrate t he existence of a novel COP9 signalosome-directed c-Jun activation pathway.