MLKL binds HSP90:CDC37

Stable Identifier
Reaction [binding]
Homo sapiens
MLKL+ HSP90 homodimer + CDC37 homodimer => MLKL:HSP90:CDC37
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The pseudokinase mixed lineage kinase domain-like (MLKL), is the terminal known obligatory effector in the necroptosis pathway, and is activated following phosphorylation by receptor interacting protein kinase-3 (RIPK3). Activated MLKL translocates to membranes, leading to membrane destabilisation and subsequent cell death. Heat‑shock protein 90 (HSP90) and cell division cycle 37 (CDC37) cochaperone complex contributes to activation of MLKL (Jacobsen AV et al. 2016; Zhao XM et al. 2016; Bigenzahn JW et al. 2016). Whether HSP90 exerts its effects on MLKL folding, oligomerization, or translocation to membranes has not been precisely determined, although it is plausible HSP90 impacts each of these activation steps (Murphy JM 2020).

Literature References
PubMed ID Title Journal Year
26866270 Hsp90 modulates the stability of MLKL and is required for TNF-induced necroptosis

Jiang, SH, Chen, Z, Hou, JJ, Jia, XL, Pu, YF, Zhang, SQ, Zhao, JB, Zhang, PP, Zhao, XM, Cui, YM

Cell Death Dis 2016
26775703 HSP90 activity is required for MLKL oligomerisation and membrane translocation and the induction of necroptotic cell death

Petrie, EJ, Jacobsen, AV, Lowes, KN, van Delft, MF, Tanzer, MC, Zhang, JG, Liu, Z, Lessene, G, Conos, SA, Murphy, JM, Huang, DC, Hildebrand, JM, Silke, J, Lucet, IS

Cell Death Dis 2016
26933192 An Inducible Retroviral Expression System for Tandem Affinity Purification Mass-Spectrometry-Based Proteomics Identifies Mixed Lineage Kinase Domain-like Protein (MLKL) as an Heat Shock Protein 90 (HSP90) Client

Zuber, J, Fauster, A, Bigenzahn, JW, Bennett, KL, Rebsamen, M, Superti-Furga, G, Gstaiger, M, Kandasamy, RK, Scorzoni, S, Vladimer, GI, Müller, AC

Mol. Cell Proteomics 2016
Orthologous Events
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