Reactome | MLKL binds HSP90:CDC37

MLKL binds HSP90:CDC37

Stable Identifier

R-HSA-9698844

Type

Reaction [binding]

Species

Homo sapiens

Compartment

cytosol

Synonyms

MLKL+ HSP90 homodimer + CDC37 homodimer => MLKL:HSP90:CDC37

ReviewStatus

5/5

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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). It remains unclear whether HSP90 influences MLKL folding, oligomerization, or membrane translocation, though it is plausible that HSP90 affects all 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 Zhao, XM, Chen, Z, Zhao, JB, Zhang, PP, Pu, YF, Jiang, SH, Hou, JJ, Cui, YM, Jia, XL, Zhang, SQ	Cell Death Dis	2016
26775703	HSP90 activity is required for MLKL oligomerisation and membrane translocation and the induction of necroptotic cell death Jacobsen, AV, Lowes, KN, Tanzer, MC, Lucet, IS, Hildebrand, JM, Petrie, EJ, van Delft, MF, Liu, Z, Conos, SA, Zhang, JG, Huang, DC, Silke, J, Lessene, G, Murphy, JM	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 Bigenzahn, JW, Fauster, A, Rebsamen, M, Kandasamy, RK, Scorzoni, S, Vladimer, GI, Müller, AC, Gstaiger, M, Zuber, J, Bennett, KL, Superti-Furga, G	Mol. Cell Proteomics	2016