Rigosertib-Activated JNK1/2 Eliminate Tumor Cells through p66Shc Activation
Julia K. Günther,
Aleksandar Nikolajevic,
Susanne Ebner,
Jakob Troppmair,
Sana Khalid
Affiliations
Julia K. Günther
Daniel Swarovski Research Laboratory (DSL), Department of Visceral, Transplant and Thoracic Surgery (VTT), Medical University Innsbruck (MUI), 6020 Innsbruck, Austria
Aleksandar Nikolajevic
Daniel Swarovski Research Laboratory (DSL), Department of Visceral, Transplant and Thoracic Surgery (VTT), Medical University Innsbruck (MUI), 6020 Innsbruck, Austria
Susanne Ebner
Daniel Swarovski Research Laboratory (DSL), Department of Visceral, Transplant and Thoracic Surgery (VTT), Medical University Innsbruck (MUI), 6020 Innsbruck, Austria
Jakob Troppmair
Daniel Swarovski Research Laboratory (DSL), Department of Visceral, Transplant and Thoracic Surgery (VTT), Medical University Innsbruck (MUI), 6020 Innsbruck, Austria
Sana Khalid
Daniel Swarovski Research Laboratory (DSL), Department of Visceral, Transplant and Thoracic Surgery (VTT), Medical University Innsbruck (MUI), 6020 Innsbruck, Austria
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.
