Proc Natl Acad Sci U S A 1996,
PMID: 8962078
Srinivasula, S M; Ahmad, M; Fernandes-Alnemri, T; Litwack, G; Alnemri, E S
The Fas/APO-1-receptor associated cysteine protease Mch5 (MACH/FLICE) is believed to be the enzyme responsible for activating a protease cascade after Fas-receptor ligation, leading to cell death. The Fas-apoptotic pathway is potently inhibited by the cowpox serpin CrmA, suggesting that Mch5 could be the target of this serpin. Bacterial expression of proMch5 generated a mature enzyme composed of two subunits, which are derived from the pre-cursor proenzyme by processing at Asp-227, Asp-233, Asp-391, and Asp-401. We demonstrate that recombinant Mch5 is able to process/activate all known ICE/Ced-3-like cysteine proteases and is potently inhibited by CrmA. This contrasts with the observation that Mch4, the second FADD-related cysteine protease that is also able to process/activate all known ICE/Ced-3-like cysteine proteases, is poorly inhibited by CrmA. These data suggest that Mch5 is the most upstream protease that receives the activation signal from the Fas-receptor to initiate the apoptotic protease cascade that leads to activation of ICE-like proteases (TX, ICE, and ICE-relIII), Ced-3-like proteases (CPP32, Mch2, Mch3, Mch4, and Mch6), and the ICH-1 protease. On the other hand, Mch4 could be a second upstream protease that is responsible for activation of the same protease cascade in CrmA-insensitive apoptotic pathways.
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Manually curated Databases
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IRef Biogrid Interaction:
CASP7
—
CASP10
(direct interaction, enzymatic study)
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IRef Biogrid Interaction:
CASP4
—
CASP10
(direct interaction, enzymatic study)
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IRef Biogrid Interaction:
CASP10
—
CASP10
(direct interaction, enzymatic study)
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IRef Biogrid Interaction:
CASP9
—
CASP10
(direct interaction, enzymatic study)
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IRef Biogrid Interaction:
CASP8
—
CASP1
(direct interaction, enzymatic study)
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IRef Biogrid Interaction:
CASP10
—
CASP1
(direct interaction, enzymatic study)
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IRef Biogrid Interaction:
CASP7
—
CASP8
(direct interaction, enzymatic study)
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IRef Biogrid Interaction:
CASP2
—
CASP10
(direct interaction, enzymatic study)
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IRef Biogrid Interaction:
CASP4
—
CASP8
(direct interaction, enzymatic study)
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IRef Biogrid Interaction:
CASP2
—
CASP8
(direct interaction, enzymatic study)
-
IRef Biogrid Interaction:
CASP9
—
CASP8
(direct interaction, enzymatic study)
-
IRef Biogrid Interaction:
CASP8
—
CASP8
(direct interaction, enzymatic study)
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IRef Biogrid Interaction:
CASP3
—
CASP10
(direct interaction, enzymatic study)
-
IRef Biogrid Interaction:
CASP10
—
CASP6
(direct interaction, enzymatic study)
-
IRef Biogrid Interaction:
CASP8
—
CASP10
(direct interaction, enzymatic study)
-
IRef Biogrid Interaction:
CASP3
—
CASP8
(direct interaction, enzymatic study)
-
IRef Biogrid Interaction:
CASP8
—
CASP6
(direct interaction, enzymatic study)
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IRef Hprd Interaction:
CASP7
—
CASP10
(in vitro)
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IRef Hprd Interaction:
CASP4
—
CASP10
(in vitro)
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IRef Hprd Interaction:
CASP9
—
CASP10
(in vitro)
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IRef Hprd Interaction:
CASP10
—
CASP2
(in vitro)
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IRef Hprd Interaction:
CASP6
—
CASP10
(in vitro)
In total, 17 gene pairs are associated to this article in curated databases