• Interaction

    AccNo. 44308 Score 0.49
    Name PM_10229667
    Kd 1.0

    Peptide

    AccNo. 44186
    Name YVAD
    Sequence YVAD
    44186_small
    Internalized no
    Is Motif no

    Interactor

    AccNo. 43808
    Name unknown

    Experiment

    AccNo. 44150
    Classification incorrect?
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    Voting_motivation
    CA CVD DM APO ANG MI BD
    0.52 0.79 0.51 1.00 0.23 0.14 0.33 Vote
    plus plus plus plus plus plus plus Yes
    minus minus minus minus minus minus minus No
    Name PM_10229667
    Detection unspecified method, MI:0686
    Source Pubmed Text Id 10229667
    Journal Biochem J. 1999 May 15;340 ( Pt 1):127-33.
    Title Inhibition of ubiquitin-proteasome pathway activates a caspase-3-like protease and induces Bcl-2 cleavage in human M-07e leukaemic cells.
    Authors Zhang XM, Lin H, Chen C, Chen BD
    Text The ubiquitin-proteasome pathway is the principal mechanism for the degradation of short-lived proteins in eukaryotic cells. Here we examine the possibility that ubiquitin-proteasome is involved in regulating the levels of Bcl-2, which is abundantly expressed in M-07e cells, a granulocyte/macrophage colony-stimulating factor (GM-CSF)-dependent human leukaemic cell line. Apoptosis in M-07e cells, induced by GM-CSF withdrawal, was associated with a gradual cleavage of Bcl-2 into a 22 kDa fragment. Treatment of M-07e cells with benzyloxycarbonyl-Leu-Leu-l-leucinal (Z-LLL-CHO; MG-132), a reversible ubiquitin-proteasome inhibitor, markedly accelerated the cleavage of Bcl-2 and promoted cell death through the apoptotic pathway. The cleavage of Bcl-2 was inhibited by a caspase-3 (CPP32)-specific inhibitor [acetyl-Asp-Glu-Val-Asp-CHO (DEVD-CHO)] but not caspase 1 inhibitor (acetyl-Tyr-Val-Ala-Asp-CHO), suggesting that Bcl-2 is a proteolytic substrate of a caspase-3-like protease activated during apoptosis. The simultaneous addition of recombinant human GM-CSF (rhGM-CSF) to M-07e cultures delayed the activation of caspase 3 and Bcl-2 cleavage triggered by Z-LLL-CHO, suggesting that the activation of the GM-CSF signalling pathway can partly overcome the apoptotic effect induced by Z-LLL-CHO. Apoptosis induced by inhibition of the proteasome pathway was verified in studies with lactacystin, a highly specific and irreversible proteasome inhibitor. Lactacystin-induced apoptosis in M-07e cells was remarkably similar to that induced by Z-LLL-CHO, which included caspase 3 activation, cleavage of Bcl-2 into a 22 kDa fragment and, ultimately, cell death. These results showed that inhibition of the ubiquitin-proteasome pathways can lead to the activation of a DEVD-CHO-sensitive caspase and induces Bcl-2 cleavage, which might have a role in mediating apoptosis in M-07e cells.
    Mesh Terms Acetylcysteine/analogs & derivatives; Acetylcysteine/pharmacology; Apoptosis/drug effects; Caspase 3; Caspases/antagonists & inhibitors; Caspases/metabolism; Cysteine Endopeptidases/metabolism; Cysteine Proteinase Inhibitors/pharmacology; Enzyme Activation/drug effects; Enzyme Precursors/metabolism; Granulocyte Macrophage Colony-Stimulating Factors, Recombinant/pharmacology; Humans; Leukemia; Leupeptins/antagonists & inhibitors; Leupeptins/pharmacology; Molecular Weight; Multienzyme Complexes/metabolism; Oligopeptides/pharmacology; Proteasome Endopeptidase Complex; Proto-Oncogene Proteins c-bcl-2/metabolism; Signal Transduction/drug effects; Time Factors; Tumor Cells, Cultured; Ubiquitins/antagonists & inhibitors; Ubiquitins/metabolism
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