-
Interaction
| AccNo. |
54213 |
Score |
0.49 |
| Name |
PM_8892627 |
| Kd |
1.0 |
|
Peptide
| AccNo. |
54091 |
| Name |
YVAD |
| Sequence |
YVAD
|
| Internalized |
no |
| Is Motif |
no |
|
Interactor
| AccNo. |
53713 |
| Name |
unknown |
|
Experiment
| AccNo. |
54055 |
Classification incorrect?
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is used to improve the automatic classification.
|
| CA |
CVD |
DM |
APO |
ANG |
MI |
BD |
|
| 0.81 |
0.59 |
0.31 |
0.99 |
0.39 |
0.04 |
0.33 |
Vote |
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 |
 |
 |
 |
Yes |
 |
 |
 |
 |
 |
 |
 |
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 |
|