2.2.2 RIPK3
Compared with RIPK1,RIPK3 bears a carboxy-terminal region that harbors
a RHIM but lacks a DD (He and Wang 2018). In addition, RIPK3 has the
similar kinase-dependent function with RIPK1 including necroptosis,
pro-inflammatory gene expression and sustained translation (Cho et al.
2009, Zhang et al. 2009, Newton et al. 2014). Activation of RIPK3 is a
vital procedure in the enablement of necroptosis. The activated RIPK1
interact with RIPK3 to form a heterodimeric amyloid structure named
necrosome complex by their respective RHIM domains (Li et al. 2012).
This process can phosphorylate RIPK3 at Ser227 for human RIPK3 or at
Thr231 and Ser232 for mouse RIPK3 and leading to activation of RIPK3.
Caspase-8 can cleave RIPK3 at Asp328, leading to its inactivation of
kinase-dependent activities (Feng et al. 2007). In addition, RIPK3
kinase triggers necroptosis through a pseudo-kinase
MLKL.