Expression, Refolding, and Autocatalytic Proteolytic Processing of the Interleukin-1β-converting Enzyme Precursor

Ramage, Paul; Cheneval, Dominique; Chvei, Maria; Graff, Patrick; Hemmig, R.; Heng, Richard; Kocher, Hans P.; MacKenzie, Andrew; Memmert, Klaus; Révész, Láśzló; Wishart, William L.

doi:10.1074/jbc.270.16.9378

Cited by 110 publications

(87 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, the mechanism underlying the activation of caspase-1 upon stimulation of TLR4 with LPS is still unclear. Our present study may allow us to propose that an unknown adaptor molecule other than MyD88 is recruited by the TIR domain located in TLR4 to activate precursor caspase-11, a possible upstream caspase for caspase-1 (23), or directly pro-caspase-1 (22), consequently leading to the activation of caspase-1. This is the first report to demonstrate that IL-18 is secreted from LPS-activated Kupffer cells via two distinctly regulated pathways.…”

Section: Discussionmentioning

confidence: 86%

See 1 more Smart Citation

Lipopolysaccharide-Induced IL-18 Secretion from Murine Kupffer Cells Independently of Myeloid Differentiation Factor 88 That Is Critically Involved in Induction of Production of IL-12 and IL-1β

Seki¹,

Tsutsui²,

Nakano³

et al. 2001

The Journal of Immunology

224

179

View full text Add to dashboard Cite

IL-18, produced as biologically inactive precursor, is secreted from LPS-stimulated macrophages after cleavage by caspase-1. In this study, we investigated the mechanism underlying caspase-1-mediated IL-18 secretion. Kupffer cells constantly stored IL-18 and constitutively expressed caspase-1. Inhibition of new protein synthesis only slightly reduced IL-18 secretion, while it decreased and abrogated their IL-1β and IL-12 secretion, respectively. Kupffer cells deficient in Toll-like receptor (TLR) 4, an LPS-signaling receptor, did not secrete IL-18, IL-1β, and IL-12 upon LPS stimulation. In contrast, Kupffer cells lacking myeloid differentiation factor 88 (MyD88), an adaptor molecule for TLR-mediated-signaling, secreted IL-18 without IL-1β and IL-12 production in a caspase-1-dependent and de novo synthesis-independent manner. These results indicate that MyD88 is essential for IL-12 and IL-1β production from Kupffer cells while their IL-18 secretion is mediated via activation of endogenous caspase-1 without de novo protein synthesis in a MyD88-independent fashion after stimulation with LPS. In addition, infection with Listeria monocytogenes, products of which have the capacity to activate TLR, increased serum levels of IL-18 in wild-type and MyD88-deficient mice but not in caspase-1-deficient mice, whereas it induced elevation of serum levels of IL-12 in both wild-type and caspase-1-deficient mice but not in MyD88-deficient mice. Taken together, these results suggested caspase-1-dependent, MyD88-independent IL-18 release in bacterial infection.

show abstract

Section: Discussionmentioning

confidence: 86%

“…Caspase-1, like other caspases, is produced as a biologically inactive precursor (pro-caspase-1), which becomes enzymatically active after appropriate cleavage (22,23). Although LPS has been demonstrated to activate caspase-1 in human macrophages, the requirement of TLR4 and/or MyD88 for the activation of caspase-1 is still to be elucidated (24).…”

mentioning

confidence: 99%

Lipopolysaccharide-Induced IL-18 Secretion from Murine Kupffer Cells Independently of Myeloid Differentiation Factor 88 That Is Critically Involved in Induction of Production of IL-12 and IL-1β

Seki¹,

Tsutsui²,

Nakano³

et al. 2001

The Journal of Immunology

224

179

View full text Add to dashboard Cite

show abstract

“…Purified GSDMD was frozen in small aliquots in liquid N 2 . Human caspase‐1, caspase‐3, and caspase‐8 were cloned into pET22 expression vectors, expressed as inclusion bodies in E. coli , and refolded as previously described (Ramage et al , 1995). Briefly, inclusion bodies were solubilized in 8M urea, and protein was refolded by rapid dilution; during which the enzymes auto‐activated.…”

Section: Methodsmentioning

confidence: 99%

GSDMD membrane pore formation constitutes the mechanism of pyroptotic cell death

et al. 2016

View full text Add to dashboard Cite

Pyroptosis is a lytic type of cell death that is initiated by inflammatory caspases. These caspases are activated within multi‐protein inflammasome complexes that assemble in response to pathogens and endogenous danger signals. Pyroptotic cell death has been proposed to proceed via the formation of a plasma membrane pore, but the underlying molecular mechanism has remained unclear. Recently, gasdermin D (GSDMD), a member of the ill‐characterized gasdermin protein family, was identified as a caspase substrate and an essential mediator of pyroptosis. GSDMD is thus a candidate for pyroptotic pore formation. Here, we characterize GSDMD function in live cells and in vitro. We show that the N‐terminal fragment of caspase‐1‐cleaved GSDMD rapidly targets the membrane fraction of macrophages and that it induces the formation of a plasma membrane pore. In vitro, the N‐terminal fragment of caspase‐1‐cleaved recombinant GSDMD tightly binds liposomes and forms large permeability pores. Visualization of liposome‐inserted GSDMD at nanometer resolution by cryo‐electron and atomic force microscopy shows circular pores with variable ring diameters around 20 nm. Overall, these data demonstrate that GSDMD is the direct and final executor of pyroptotic cell death.

show abstract

“…Asp-103, Asp-119, Asp-297 and Asp-316, arise at Asp-Xaa bonds (Figure 3), suggesting that active caspase-1 may be derived by autoproteolysis [33,34]. Following the initial cleavage at Asp-297-Ser-298, autoproteolysis occurs in a series of steps, generating fragments of increasing activity and eventually producing p20\p10 ICE [35,36]. Caspase-1 is found predominantly in the cytoplasm of cells as the p45 pro-form [37], although some is also localized to the external cell surface membrane, where it activates pro-IL-1β to its mature form during secretion [38].…”

Section: Structure and Functionmentioning

confidence: 99%

Caspases: the executioners of apoptosis

Cohen

1997

Biochemical Journal

4,323

2,952

View full text Add to dashboard Cite

Apoptosis is a major form of cell death, characterized initially by a series of stereotypic morphological changes. In the nematode Caenorhabditis elegans, the gene ced-3 encodes a protein required for developmental cell death. Since the recognition that CED-3 has sequence identity with the mammalian cysteine protease interleukin-1β-converting enzyme (ICE), a family of at least 10 related cysteine proteases has been identified. These proteins are characterized by almost absolute specificity for aspartic acid in the P " position. All the caspases (ICE-like proteases) contain a conserved QACXG (where X is R, Q or G) pentapeptide activesite motif. Caspases are synthesized as inactive proenzymes comprising an N-terminal peptide (prodomain) together with one large and one small subunit. The crystal structures of both caspase-1 and caspase-3 show that the active enzyme is a heterotetramer, containing two small and two large subunits. Activation of caspases during apoptosis results in the cleavage of critical cellular substrates, including poly(ADP-ribose) poly-

show abstract

Expression, Refolding, and Autocatalytic Proteolytic Processing of the Interleukin-1β-converting Enzyme Precursor

Cited by 110 publications

References 21 publications

Lipopolysaccharide-Induced IL-18 Secretion from Murine Kupffer Cells Independently of Myeloid Differentiation Factor 88 That Is Critically Involved in Induction of Production of IL-12 and IL-1β

Lipopolysaccharide-Induced IL-18 Secretion from Murine Kupffer Cells Independently of Myeloid Differentiation Factor 88 That Is Critically Involved in Induction of Production of IL-12 and IL-1β

GSDMD membrane pore formation constitutes the mechanism of pyroptotic cell death

Caspases: the executioners of apoptosis

Contact Info

Product

Resources

About