Reactome | SARS-CoV-1 nsp3 deubiquinates K48-linked pUb IkBA

SARS-CoV-1 nsp3 deubiquinates K48-linked pUb IkBA

Stable Identifier

R-HSA-9711058

Type

Reaction [omitted]

Species

Homo sapiens

Related Species

Human SARS coronavirus

Compartment

cytosol, double membrane vesicle viral factory outer membrane

ReviewStatus

5/5

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Disease (Homo sapiens)

- Infectious disease (Homo sapiens)
  - Viral Infection Pathways (Homo sapiens)
    - SARS-CoV Infections (Homo sapiens)
      - SARS-CoV-1 Infection (Homo sapiens)
        
        SARS-CoV-1-host interactions (Homo sapiens)
        
        SARS-CoV-1 activates/modulates innate immune responses (Homo sapiens)
        
        SARS-CoV-1 nsp3 deubiquinates K48-linked pUb IkBA (Homo sapiens)

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SARS-CoV-1 nsp3 deubiquinates K48-linked pUb IkBA

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Severe acute respiratory syndrome coronavirus type 1 (SARS-CoV-1) 1a-encoded papain-like protease (PLPro or nsp3) is primarily involved in SARS-CoV replication. In addition, viral nsp3 removes ubiquitin (Ub) and ISG15 proteins from host cell proteins by recognizing a consensus motif LXGG (Lindner HA et al. 2005; Barretto N et al. 2005; Ratia K et al. 2006). Structural and biochemical studies revealed that SARS-CoV-1 nsp3 targets at least two Ub binding sites, S2 and S1, to cleave Lys48-linked polyUb chains on substrates (Békés M et al. 2016). The processing of Lys48-linked polyUb chains from NF-kappa-B inhibitor alpha (NFKBIA or IκBα) in TNF-α-treated HeLa cell lysates by SARS nsp3 led to an increase in di- and monoUb-conjugated forms of NFKBIA (IκBα) (Békés M et al. 2016). Similar results were obtained upon co-expression of NFKBIA and viral nsp3 in human embryonic kidney HEK293 cells (Ratia K et al. 2014). The data suggest that SARS-CoV-1 nsp3 inhibits the nuclear factor kappa B (NFκappaB) activation by delaying 26S proteasome-dependent degradation of ubiquitinated NFKBIA (IκBα).

Literature References

PubMed ID	Title	Journal	Year
27203180	Recognition of Lys48-Linked Di-ubiquitin and Deubiquitinating Activities of the SARS Coronavirus Papain-like Protease Békés, M, Huang, TT, Ekkebus, R, Ovaa, H, Lima, CD, van der Heden van Noort, GJ	Mol Cell	2016
27164085	SARS Coronavirus Papain-Like Protease Inhibits the TLR7 Signaling Pathway through Removing Lys63-Linked Polyubiquitination of TRAF3 and TRAF6 Jou, YJ, Wang, CY, Huang, SH, Li, SW, Wan, L, Lin, CW, Kung, SH, Lin, YJ, Hsiao, LH	Int J Mol Sci	2016
24854014	Structural Basis for the Ubiquitin-Linkage Specificity and deISGylating activity of SARS-CoV papain-like protease Báez-Santos, YM, Baker, SC, Kilianski, A, Mesecar, A, Ratia, K	PLoS Pathog	2014
25764917	SARS hCoV papain-like protease is a unique Lys48 linkage-specific di-distributive deubiquitinating enzyme Drag, M, Békés, M, Mulder, MP, Huang, TT, Ovaa, H, Kasperkiewicz, P, Lima, CD, Rut, W	Biochem J	2015