JNK-signaling: A multiplexing hub in programmed cell death
Danny N. Dhanasekaran1 and E. Premkumar Reddy2
1 Department of Cell Biology, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma, OK, USA
2 Department of Oncological Sciences, and Department of Structural and Chemical Biology, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Correspondence:
Danny N. Dhanasekaran, email:
Correspondence:
E. Premkumar Reddy, email:
Keywords: JNK, apoptosis, cell death, necroptosis, ferroptosis
Received: September 11, 2017 Accepted: October 28, 2017 Published: November 02, 2017
Abstract
Jun N-terminal kinases or JNKs have been shown to be involved in a wide array of signaling events underlying tumorigenesis and tumor progression. Through its interaction with a diverse set of signaling proteins and adaptors, JNKs regulate cell proliferation, invasive migration, therapy resistance, and programmed cell death. JNKs have been shown to play a role in apoptotic as well as non-apoptotic programmed cell death mechanisms including those of necroptosis, ferroptosis, pyroptosis, and autophagy. Most of the tumorigenic regulatory functions of JNKs can be related to their ability to module cell death via these programmed cell death mechanisms. JNKs stimulate or inhibit cell death in a context-dependent manner by stimulating the expression of specific genes as well as by modulating the activities of pro- and anti-apoptotic proteins through distinct phosphorylation events. This review summarizes our current understanding of the role of JNK in programmed cell death and its impact on cancer growth, progression, and therapy.
