|
KMID : 0613820160260070868
|
|
Journal of Life Science
2016 Volume.26 No. 7 p.868 ~ p.874
|
|
|
Functional and Physiological Characteristic of RIPK and MLKL in TNF Signaling
|
|
Park Young-Hoon
Jeong Mi-Suk
Jang Se-Bok
|
|
|
Abstract
|
|
|
|
Receptor-interacting protein kinase 1 (RIPK1) and RIPK3 are members of the serine or threonine protein kinase superfamily that phosphorylates the hydroxyl group of serine or threonine through the highly conserved kinase region. The RIPK family plays a crucial role not only in inflammation and innate immunity, but also in mediating programmed cell death, such as apoptosis and necroptosis. The interaction between RIPK1 and other TNFR1-related proteins has been shown to assemble a signaling complex I that controls activation of the pro-survival transcription factor NF-κB upon binding of cytokines to TNF receptor 1 (TNFR1). Moreover, RIPK1 and RIPK3 interact through their RIP homotypic interaction motifs (RHIMs) to mediate programmed necrosis, which has long been considered an accidental and uncontrolled cell death form with morphological characteristics differing from those of apoptosis. Highly conserved sequences of RHIM in RIPK1 and RIPK3 were shown to regulate their binary interaction, leading to assembly of a cytosolic amyloid complex termed the “necrosome”. The necrosome also contains mixed lineage kinase domain-like protein (MLKL), which has been found recently to be a substrate of RIPK3 to mediate downstream signaling. This review provides an overview of the functional and physiological characteristics of RIPKs and MLKL in TNF signaling.
|
|
|
KEYWORD
|
|
|
MLKL, programmed cell death, RHIM, RIPK, TNF signaling
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
|