Special Session 106: Data-Driven Multiscale Modeling and Model Reduction Techniques in Biomedicine: Bridging Scales and Complexity

Spatio-temporal Dynamics of MMK4 Function for JNK Pathway from Analog to Digital Converter in Response to Stress Intensities

Nuha Loling Othman
Osaka University
Japan
Co-Author(s):    Hisashi Moriizumi, Mutsuhiro Takekawa, Takashi Suzuki
Abstract:
Spatio-temporal regulation of mitogen-activated protein kinase (MAPK) signaling is essential for mammalian cells` growth, differentiation, and survival. There are three mitogens involved in response to proliferation, apoptosis, and cytokine production, which are called ERK, p38, and c-JUN N-terminal kinases (JNK). MAPK pathway cascade is a central signal transduction pathway activated by growth factors in response to stimuli by phosphorylating and activating mitogen-activated protein kinase kinase kinase (MAPKKK) - mitogen-activated protein kinase kinase (MAPKK) - MAPK in a stepwise and continuous manner, transmitting signals from upstream to downstream. The activation of MAPK which activates several nuclear targets such as mitogen-activated protein kinase kinase 4 (MKK4) which binds to JNK leads to their translocation from cytoplasm to nucleus. MKK4 is a member of MAPKK family, phosphorylates, and activates JNK in response to cellular stresses and proinflammatory cytokines. JNK which also belongs to the family of mitogen-activated protein kinase (MAPK) has been implicated in the apoptotic response of cancer cells exposed to stress while JNK is required to induce apoptosis. Here, we model the relation of MAPK pathway response to stress intensities for apoptosis in programmed cell death in cancer.