A novel small molecule deubiquitinase inhibitor blocks Jak2 signaling through Jak2 ubiquitination

► WP1130 is a more potent inhibitor of Jak2 signaling than its parent compound AG490. ► WP1130 induces formation of K63-linked ubiquitin polymers on Jak2. ► Jak2 ubiquitination by WP1130 results in its trafficking to perinuclear aggresomes. ► WP1130 inhibits a deubiquitinase (DUB) specific for Jak2 ubiquitin.