Specific cleavage of Mcl-1 by caspase-3 in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in Jurkat leukemia T cells.
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces programmed cell death through the caspase activation cascade and translocation of cleaved Bid (tBid) by the apical caspase-8 to mitochondria to induce oligomerization of multidomain Bax and Bak. However, the roles of prosurvival Bcl-2 family proteins in TRAIL apoptosis remain elusive. Here we ... showed that, besides the specific cleavage and activation of Bid by caspase-8 and caspase-3, TRAIL-induced apoptosis in Jurkat T cells required the specific cleavage of Mcl-1 at Asp-127 and Asp-157 by caspase-3, while other prototypic antiapoptotic factors such as Bcl-2 or Bcl-X(L) seemed not to be affected. Mutation at Asp-127 and Asp-157 of Mcl-1 led to cellular resistance to TRAIL-induced apoptosis. In sharp contrast to cycloheximide-induced Mcl-1 dilapidation, TRAIL did not activate proteasomal degradation of Mcl-1 in Jurkat cells. We further established for the first time that the C-terminal domain of Mcl-1 became proapoptotic as a result of caspase-3 cleavage, and its physical interaction and cooperation with tBid, Bak, and voltage-dependent anion-selective channel 1 promoted mitochondrial apoptosis. These results suggested that removal of N-terminal domains of Bid by caspase-8 and Mcl-1 by caspase-3 enabled the maximal mitochondrial perturbation that potentiated TRAIL-induced apoptosis.
Mesh Terms:
Amino Acid Sequence, Animals, Apoptosis, Apoptosis Regulatory Proteins, Aspartic Acid, BH3 Interacting Domain Death Agonist Protein, Binding Sites, Carrier Proteins, Caspase 3, Caspase 8, Caspases, Cell Death, Cell Line, Tumor, Cell Survival, Cycloheximide, Cytochromes c, Down-Regulation, Glutathione Transferase, Hela Cells, Humans, Immunoprecipitation, Jurkat Cells, Leukemia, Membrane Glycoproteins, Microscopy, Fluorescence, Mitochondria, Molecular Sequence Data, Mutagenesis, Site-Directed, Mutation, Neoplasm Proteins, Plasmids, Point Mutation, Proteasome Endopeptidase Complex, Protein Structure, Tertiary, Protein Synthesis Inhibitors, Proto-Oncogene Proteins c-bcl-2, RNA, Messenger, RNA, Small Interfering, Rats, Reticulocytes, Reverse Transcriptase Polymerase Chain Reaction, TNF-Related Apoptosis-Inducing Ligand, Tumor Necrosis Factor-alpha, bcl-X Protein
Amino Acid Sequence, Animals, Apoptosis, Apoptosis Regulatory Proteins, Aspartic Acid, BH3 Interacting Domain Death Agonist Protein, Binding Sites, Carrier Proteins, Caspase 3, Caspase 8, Caspases, Cell Death, Cell Line, Tumor, Cell Survival, Cycloheximide, Cytochromes c, Down-Regulation, Glutathione Transferase, Hela Cells, Humans, Immunoprecipitation, Jurkat Cells, Leukemia, Membrane Glycoproteins, Microscopy, Fluorescence, Mitochondria, Molecular Sequence Data, Mutagenesis, Site-Directed, Mutation, Neoplasm Proteins, Plasmids, Point Mutation, Proteasome Endopeptidase Complex, Protein Structure, Tertiary, Protein Synthesis Inhibitors, Proto-Oncogene Proteins c-bcl-2, RNA, Messenger, RNA, Small Interfering, Rats, Reticulocytes, Reverse Transcriptase Polymerase Chain Reaction, TNF-Related Apoptosis-Inducing Ligand, Tumor Necrosis Factor-alpha, bcl-X Protein
J. Biol. Chem.
Date: Mar. 18, 2005
PubMed ID: 15637055
View in: Pubmed Google Scholar
Download Curated Data For This Publication
73986
Switch View:
- Interactions 7