Reactome | SGT1:HSP90 binds inactive NLRP3

SGT1:HSP90 binds inactive NLRP3

Stable Identifier

R-HSA-873951

Type

Reaction [binding]

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

Locations in the PathwayBrowser

Expand all

Disease (Homo sapiens)

- Infectious disease (Homo sapiens)
  - Parasitic Infection Pathways (Homo sapiens)
    - Leishmania infection (Homo sapiens)
      - Cell recruitment (pro-inflammatory response) (Homo sapiens)
        
        Purinergic signaling in leishmaniasis infection (Homo sapiens)
        
        SGT1:HSP90 binds inactive NLRP3 (Homo sapiens)

General

SBML | | PDF

SVG | | PPTX | SBGN

Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

SGT1 and HSP90 bind the NLRP3 (NALP3) LRR domain. Genetic studies in plants suggest a role for SGT1-HSP90 as co-chaperones of plant resistance (R) proteins, serving to maintain them in an inactive but signaling-competent state. R-protein activation is beleived to lead to dissociation of the SGT1-HSP90 complex. SGT1 and HSP90 are highly conserved, while R proteins are structurally related to mammalian NLRs. Human SGT1 and HSP90 were found to bind NLRP3 (Mayor et al. 2007). Knockdown of human SGT1 by small interfering RNA or chemical inhibition of HSP90 by geldanamycin abrogated NLRP3 inflammasome activity in human monocytic cell line THP-1 (Mayor et al. 2007). Similarly, NLRP3 inflammasome activation was abrogated in geldanamycin-treated human retinal pigment epithelial (RPE) cells (Piippo N et al. 2018). These data indicate that SGT1 and HSP90 are involved in regulation of NLRP3 inflammasome signaling (Mayor et al. 2007; Piippo N et al. 2018).

Literature References

PubMed ID	Title	Journal	Year
17435760	A crucial function of SGT1 and HSP90 in inflammasome activity links mammalian and plant innate immune responses Mayor, A, Martinon, F, De Smedt, T, Pétrilli, V, Tschopp, J	Nat Immunol	2007
29712950	Hsp90 inhibition as a means to inhibit activation of the NLRP3 inflammasome Piippo, N, Korhonen, E, Hytti, M, Skottman, H, Kinnunen, K, Josifovska, N, Petrovski, G, Kaarniranta, K, Kauppinen, A	Sci Rep	2018