JAB1 interacts with both the progesterone receptor and SRC-1

JAB1 (Jun activation domain-binding protein-1) has previously been describe d as a coactivator of AP1 transcription factor. We show here, by yeast and mammalian two-hybrid analyses and by pull-down experiments, that JAB1 also interacts with both the progesterone receptor (PR) and the steroid receptor coactivator 1 (SRC-1) and that it stabilizes PR-SRC-1 complexes. We also s how that JAB1 potentiates the activity of a variety of transcription factor s known to associate with SRC-1 (nuclear receptors, activator protein-1, an d nuclear factor KB). This occurs without any modification of PR or SRC-1 c oncentration. JAB1 is a subunit of a large multiprotein complex that has be en called the COP9 signalosome. The latter is present in plant and animal c ells and has been shown to be involved in a variety of cellular mechanisms including transcription regulation, cell cycle control, and phosphorylation cascades. We now show that it is also involved in the mechanisms of action of nuclear receptors and of their coactivators.