Crystal structure of the cysteine protease interleukin-1β-converting enzyme: A (p20/p10)2 homodimer

Walker, Nigel; Talanian, Robert V.; Brady, Kenneth D.; Dang, Luan C.; Bump, Nancy J.; Ferenza, C.R.; Franklin, Simon; Ghayur, Tariq; Hackett, Maria; Hammill, L.D.; Herzog, Linda; Hugunin, M.; Houy, W.; Mankovich, John A.; McGuiness, L.; Orlewicz, E.; Paskind, Michael; Pratt, Clifford; Reis, Pedro; Summani, A.; Terranova, Michele; Welch, Jeffrey P.; Li, Xiong; Moller, Abraham Jon; Tracey, Daniel E.; Kamen, Robert; Wong, Winnie W.

doi:10.1016/0092-8674(94)90303-4

Cited by 561 publications

(376 citation statements)

References 53 publications

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“…Ac-DVAD-FMK) bind via a thioester linkage to a transition state oxyanion and the carbonyl oxygen occupies an oxyanion hole in the caspase transition state. 59,60 Peptide inhibitors display a wide range of specificity and potency against caspase activity with dissociation constants ranging from pM to low micromolar (mM) concentrations (Table 2).…”

Section: Synthetic Caspase Inhibitorsmentioning

confidence: 99%

Caspase inhibitors: viral, cellular and chemical

2006

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Section: Synthetic Caspase Inhibitorsmentioning

confidence: 99%

Caspase inhibitors: viral, cellular and chemical

2006

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“…The mature and active form of all caspases is a heterotetrameric complex composed of two large subunits and two small subunits. 75,76 Caspases with large prodomains, eg caspase-2, -8 and -9, are thought to be involved in the initiation of the apoptotic response and are therefore called initiator caspases. Initiator caspases are directly linked to different death-inducing signaling complexes, such as the CD95/Fas signaling complex (pro-caspase-8) or the mitochondrial apoptosome (pro-caspase-9), by protein interaction motifs in their prodomains.…”

Section: Initiator and Effector Caspases And Their Targetsmentioning

confidence: 99%

The kiss of death: promises and failures of death receptors and ligands in cancer therapy

et al. 2001

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“…Inhibition of caspase-3 activity attenuates apoptosis in many mammalian cell types including neuronal cells (Nath et al, 1 9 9 6~;Posmantur et al, 1997). After apoptotic injury, the 32-kDa caspase-3 proenzyme is cleaved to 17-and 12-kDa fragments, which form the active heterodimer (Thornberry et al, 1992;Walker et al, 1994). Activated caspase-3 proteolytically cleaves important nuclear and cytoskeletal proteins during apoptosis (Fernandes-Alnemri et al, 1995;Nicholson et al, 1995;Tewari et al, 1995).…”

Section: K M Mcginnis Et Almentioning

confidence: 99%

Alterations of Extracellular Calcium Elicit Selective Modes of Cell Death and Protease Activation in SH‐SY5Y Human Neuroblastoma Cells

McGinnis¹,

Wang²,

Gnegy³

1999

Journal of Neurochemistry

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Abstract:The role of intracellular Ca2+ homeostasis in mechanisms of neuronal cell death and cysteine protease activation was investigated in SH-SY5Y human neuroblastoma cells. Cells were incubated in 2 mM EGTA to lower intracellular Ca2+ or 5 mM CaCI, to raise it. Cell death and activation of calpain and caspase-3 were measured. Both EGTA and excess CaCI, elicited cell death. EGTA induced DNA laddering and an increase in caspase-3-like, but not calpain, activity. Pan-caspase inhibitors protected against EGTA-, but not CaCI,-, induced cell death. Conversely, excess Ca2+ elicited necrosis and activated calpain but not caspase-3. Calpain inhibitors did not preserve cell viability. Ca2+ was the death-mediating factor, because restoration of extracelMar Ca2+ protected against cell death induced by EGTA and blockade of Ca2+ channels by Ni'+ protected against that induced by high Ca2+. We conclude that the EGTA treatment lowered intracellular Ca2+ and elicited caspase-3-like protease activity, which led to apoptosis. Conversely, excess extracellular Ca2+ entered Ca2+ channels and increased intracellular Ca2+ leading to calpain activation and necrosis. The mode of cell death and protease activation in response to changing Ca2+ were selective and mutually exclusive, demonstrating that these are useful models to individually investigate apoptosis and necrosis. Key Words: Apoptosis-Necrosis-Calpain-Caspase-3-Ca2+ homeostasis-Neuronal death.

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Crystal structure of the cysteine protease interleukin-1β-converting enzyme: A (p20/p10)2 homodimer

Cited by 561 publications

References 53 publications

Caspase inhibitors: viral, cellular and chemical

Caspase inhibitors: viral, cellular and chemical

The kiss of death: promises and failures of death receptors and ligands in cancer therapy

Alterations of Extracellular Calcium Elicit Selective Modes of Cell Death and Protease Activation in SH‐SY5Y Human Neuroblastoma Cells

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