JAB1 (Jun activation domain-binding protein-1) was isolated in a yeast two- hybrid screen using the c-Jun N-terminal activation domain. Binding of JAB1 to Jun potentiates activator protein transcription factor (AP-1) target gene transcription. JAB1 interacts with c-Jun and JunD, but not with JunB or v-Jun. It also interacts with other transcriptional regulatory complexes, such as the activator of stromelysin 1 gene transcription complex (RNF4/SPBP) and the steroid receptor coactivator-1 complex. Additionally, JAB1 is the CSN5 subunit of the COP9 signalosome, which contains multiple proteins with homologies to proteins present in the 19S subunit of the proteosome. Interestingly, JAB1 has been implicated in the instigation of p27kip1 and rat lutropin/choriogonadotropin receptor degradation. JAB1 has also been found to be involved in integrin signaling cascades, because it colocalizes with the integrin LFA-1 receptor and is translocated to the nucleus, where it enhances transactivation of the AP-1- dependent promoter following integrin stimulation. Thus, JAB1 is a multifunctional protein that regulates both gene transcription and protein degradation.