Any feedback?
Please rate this page
(literature.php)
(0/150)

BRENDA support

Literature summary for 3.4.22.28 extracted from

  • Loetzerich, M.; Roulin, P.S.; Boucke, K.; Witte, R.; Georgiev, O.; Greber, U.F.
    Rhinovirus 3C protease suppresses apoptosis and triggers caspase-independent cell death (2018), Cell Death Dis., 9, 272 .
    View publication on PubMedView publication on EuropePMC
Search for more literature for 3.4.22.28

Inhibitors

Inhibitors Comment Organism Structure
AG7088 3Cpro specific inhibitor, late addition of AG7088 to HeLa cells inhibits production of HRV-A16. Inhibition of 3Cpro by AG7088 early in infection (prior to onset of virion production) has stronger effects than late addition, due to inhibition of poly-protein processing rhinovirus A16
additional information no inhibition by benzyloxycarbonyl-VAD-(O-methyl)-fluoromethylketone or QVD rhinovirus A16

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
receptor-interacting protein kinase 1 + H2O rhinovirus A16 cleavage of the RIPK1 death-domain, and generation of N-terminal RIPK1 fragments ?
-
 ?

Organism

Organism UniProt Comment Textmining
rhinovirus A16
-
 HRV-A16
-

Source Tissue

Source Tissue Comment Organism Textmining
additional information HRV-A16 virus in infected HeLa cells rhinovirus A16
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
receptor-interacting protein kinase 1 + H2O cleavage of the RIPK1 death-domain, and generation of N-terminal RIPK1 fragments rhinovirus A16 ?
-
 ?
receptor-interacting protein kinase 1 + H2O in vitro cleavage of RIPK1 by 3Cpro in HeLa cell extracts, cleavage of the RIPK1 death-domain, and generation of N-terminal RIPK1 fragments. The middle p62/SQSTM1 binding domain of RIPK1 contains three strictly defined HRV 3Cpro consensus motifs [AVNTPISQ]-x-x-Q-[GNSA]-[PLDIQEVAN] at Q401, Q464, and Q573. 3Cpro cleaves parts of the middle domain and the C-terminus of RIPK1. Enzyme 3Cpro generates a 60 kDa N-terminal RIPK1 fragment rhinovirus A16 ?
-
 ?

Synonyms

Synonyms Comment Organism
3C-protease
-
 rhinovirus A16
3Cpro
-
 rhinovirus A16
rhinovirus 3C protease
-
 rhinovirus A16

General Information

General Information Comment Organism
malfunction poly I:C or puromycin-induced apoptosis is inhibited by pan-caspase inhibitors QVD or benzyloxycarbonyl-VAD-(O-methyl)-fluoromethylketone (zVADfmk) but not by the necroptosis inhibitor necrostatin 1 (NEC-1) or 3Cpro inhibitor AG7088. Catalytically inactive 3Cpro induces apoptosis, albeit to a lesser extent than poly I:C. The selective 3Cpro inhibitor AG7088 completely abrogates RIPK1 processing, and blocks viral replication as indicated by the lack of VP2 rhinovirus A16
metabolism in HRV-A16 infection, the RIPK1 complex is substantially altered due to 3Cpro, and consists of the 60 kDa RIPK1 fragment, procaspase-8, 3ABC and/or active 3Cpro and p62/SQSTM1 rhinovirus A16
additional information 3Cpro and 3C precursors are found to coimmuno-precipitate with receptor-interacting protein kinase 1 (RIPK1) cleaving the RIPK1 death-domain, and generating N-terminal RIPK1 fragments rhinovirus A16
physiological function 3Cpro controls cell death programs. 3Cpro and its precursors are key enzymes for processing the enteroviral poly-protein. 3Cpro cleaves the death kinase RIPK1, and precludes apoptotic and necroptotic cell death. Rhinoviruses suppress apoptosis and necroptosis, and release progeny by an alternative cell death pathway, which is controlled by viral proteases modifying innate immune complexes. The impairment of dsRNA-induced apoptosis late in infection is controlled by the viral 3C-protease (3Cpro), which disrupts RIPK1-TRIF/FADD/SQSTM1 immune-complexes. The expression of 3Cpro suppresses annexin V signals induced by poly I:C, whereas catalytically inactive 3Cpro induces apoptosis, albeit to a lesser extent than poly I:C. Important role of 3Cpro in suppressing apoptosis of host cells. Catalytically active 3Cpro suppresses apoptosis and enhances cell lysis in absence of other viral factors. 3Cpro generates a 60 kDa N-terminal RIPK1 fragment, and supports HRV-A16 titer production late in infection. Binding of 3ABC and 3Cpro to RIPK1-containing immuno-complexes and proteolytic processing of RIPK1 by 3Cpro interfer with death signaling rhinovirus A16