The Role of E3 ubiquitin Ligase WWP2 and the Regulation of PARP1 by Ubiquitinated Degradation in Apoptosis of Acute Lymphoblastic Leukemia

Abstract

Acute lymphoblastic leukemia (ALL) has been huge threaten for people health and finding effective target therapy is urgent and important. WWP2, as one of E3 ubiquitin ligase, is involved in many biological processes by specifically binding to substrates. PARP1 plays a role in cell apoptosis and is considered as a therapeutic target of certain cancers. In this study, we firstly tested WWP2 expression in patients and normal people and analyzed the relationship with clinicopathologic factors. We demonstrated WWP2 was involved in ALL apoptosis and knockout WWP2 alleviated ALL apoptosis induced by Dox in vitro and vivo. WWP2 negatively regulated and interacted with PARP1 in vitro and vivo and WWP2 mechanically degraded PARP1 through polyubiquitin-proteasome pathway. These findings suggested WWP2 played a role in ALL apoptosis and displayed a regulatory pathway of PARP1, which provide a new potential therapeutic target for the treatment of ALL.