Abstract
Heat shock protein 90 regulates necroptosis by modulating multiple signaling effectors.
Highlights
Necroptosis has recently been identified as a form of programmed necrosis.[1]
As RIP3 is well established as a key kinase regulating necroptosis, it is of interest to determine whether or not RIP3 is a client of heat shock protein 90 (HSP90)
It has become clear that the functions of RIP1 and RIP3 in necroptosis are modulated by HSP90
Summary
Heat shock protein 90 regulates necroptosis by modulating multiple signaling effectors. RIP3 and MLKL activation has not been fully elucidated To this end, two new studies by Jacobsen et al.[9] and Zhao et al.[10] published in the issue of Cell Death and Disease, along with recent work by Li et al.,[11] reveal that heat shock protein 90 (HSP90) regulates the stability and function of RIP3 and MLKL. A previous study has demonstrated RIP1 as an HSP90 client.[13] Inhibition of HSP90 function disrupted association between HSP90 and RIP1, and resulted in the degradation of RIP1.13 Further, loss of HSP90 activity blocked TNF-induced RIP1-dependent NF-κB activation and necrosis, and made cells sensitive to TNF-induced apoptosis.[13,14] HSP90 is a chaperone protein that is required to maintain the stability and function of RIP1 in the necroptosis pathway. Inhibition of HSP90 function prevented the oligomerization of mutant MLKL S345D and its membrane
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