Rigosertib-Activated JNK1/2 Eliminate Tumor Cells through p66Shc Activation

Biology

Jakob Troppmair¹  JuliaK. Günther¹  Aleksandar Nikolajevic¹  Sana Khalid¹  Susanne Ebner¹ 

[1] Daniel Swarovski Research Laboratory (DSL), Department of Visceral, Transplant and Thoracic Surgery (VTT), Medical University Innsbruck (MUI), 6020 Innsbruck, Austria;

关键词: p66Shc;    Rigosertib;    reactive oxygen species;    cell death;   

DOI  :  10.3390/biology9050099

来源: DOAJ

【 摘 要 】

Rigosertib, via reactive oxygen species (ROS), stimulates cJun N-terminal kinases 1/2 (JNK1/2), which inactivate RAS/RAF signaling and thereby inhibit growth and survival of tumor cells. JNK1/2 are not only regulated by ROS—they in turn can also control ROS production. The prooxidant and cell death function of p66Shc requires phosphorylation by JNK1/2. Here, we provide evidence that establishes p66Shc, an oxidoreductase, as a JNK1/2 effector downstream of Rigosertib-induced ROS production, DNA damage, and cell death. This may provide a common pathway for suppression of tumor cell growth by Rigosertib.

【 授权许可】

Unknown