• Interaction

    AccNo. 54213 Score 0.49
    Name PM_8892627
    Kd 1.0

    Peptide

    AccNo. 54091
    Name YVAD
    Sequence YVAD
    54091_small
    Internalized no
    Is Motif no

    Interactor

    AccNo. 53713
    Name unknown

    Experiment

    AccNo. 54055
    Classification incorrect?
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    Voting_motivation
    CA CVD DM APO ANG MI BD
    0.81 0.59 0.31 0.99 0.39 0.04 0.33 Vote
    plus plus plus plus plus plus plus Yes
    minus minus minus minus minus minus minus No
    Name PM_8892627
    Detection unspecified method, MI:0686
    Source Pubmed Text Id 8892627
    Journal J Immunol. 1996 Nov 1;157(9):3949-57.
    Title Intracellular IL-1beta is an inhibitor of Fas-mediated apoptosis.
    Authors Tatsuta T, Cheng J, Mountz JD
    Text Fas-mediated apoptosis has been shown to be mediated by the IL-1beta converting enzyme (ICE) pathway. To determine the relationship between ICE and its substrate IL-1beta, we examined six human cell lines for susceptibility to Fas-mediated apoptosis and Fas induction of ICE-like activity. The human B lymphoblastoid cell line SKW6.4 and the human T lymphoma cell lines Jurkat, CEM-6, H-9, and MOLT4 were susceptible to Fas-mediated apoptosis, whereas the human promyelocytic leukemia cell line HL-60 was resistant to Fas-mediated apoptosis. ICE mRNA was highly expressed in SKW6.4, H-9, and HL-60 cells, and ICE-like activity increased during Fas-mediated apoptosis in SKW6.4 cells. In contrast, IL-1beta mRNA was highly expressed only in HL-60 cells. Acetyl-Tyr-Val-Ala-Asp-chloromethylketone, a tetrapeptidyl inhibitor of ICE, prevented Fas-mediated apoptosis strongly in SKW6.4 and H-9 cells but weakly or marginally in other cells. To examine whether intracellular IL-1beta is a proteolytic substrate or an endogenous competitive inhibitor against other substrates for Fas-ICE-mediated apoptosis in SKW6.4 cells, we established precursor IL-1beta transfectant clones using SKW6.4 cells. We demonstrated that stably transfected SKW6.4 cells expressing precursor IL-1beta, but not cells transfected with the empty vector, exhibited resistance to Fas-mediated apoptosis due to competitive inhibition of ICE-like activity, which was associated with increased cleavage of precursor IL-1beta to mature IL-1beta. These results suggest that Fas-mediated apoptosis is mediated by ICE cleavage of proteolytic substrates other than IL-1beta and that IL-1beta is an endogenous inhibitor of Fas-mediated apoptosis.
    Mesh Terms Amino Acid Chloromethyl Ketones/pharmacology; Antigens, CD95/physiology; Apoptosis/physiology; B-Lymphocytes/pathology; Burkitt Lymphoma/pathology; Caspase 1; Cysteine Endopeptidases/genetics; Cysteine Endopeptidases/physiology; Enzyme Induction; HL-60 Cells; Hela Cells; Humans; Interleukin-1/pharmacology; Intracellular Fluid/metabolism; Leukemia-Lymphoma, Adult T-Cell/pathology; Lymphoma, Large B-Cell, Diffuse/pathology; Oligopeptides/pharmacology; Protease Inhibitors/pharmacology; Protein Precursors/metabolism; Recombinant Fusion Proteins/metabolism; Signal Transduction; T-Lymphocytes/pathology; Transfection; Tumor Cells, Cultured
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