TGF-beta-induced apoptosis is mediated by the adapter protein Daxx that facilitates JNK activation.

Transforming growth factor-beta (TGF-beta) is a multifunctional growth factor that has a principal role in growth control through both its cytostatic effect on many different epithelial cell types and its ability to induce programmed cell death in a variety of other cell types. Here we have used a screen for ...
proteins that interact physically with the cytoplasmic domain of the type II TGF-beta receptor to isolate the gene encoding Daxx - a protein associated with the Fas receptor that mediates activation of Jun amino-terminal kinase (JNK) and programmed cell death induced by Fas. The carboxy-terminal portion of Daxx functions as a dominant-negative inhibitor of TGF-beta-induced apoptosis in B-cell lymphomas, and antisense oligonucleotides to Daxx inhibit TGF-beta-induced apoptosis in mouse hepatocytes. Furthermore, Daxx is involved in mediating JNK activation by TGF-beta. Our findings associate Daxx directly with the TGF-beta apoptotic-signalling pathway, and make a biochemical connection between the receptors for TGF-beta and the apoptotic machinery.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Animals, Antigens, CD95, Apoptosis, COS Cells, Carrier Proteins, Cell Compartmentation, Cell Division, Hepatocytes, Humans, Intracellular Signaling Peptides and Proteins, Lymphoma, B-Cell, Mitogen-Activated Protein Kinase 8, Mitogen-Activated Protein Kinases, Nuclear Proteins, Oligonucleotides, Antisense, Protein Structure, Tertiary, Protein-Serine-Threonine Kinases, Receptors, Transforming Growth Factor beta, Signal Transduction, Transforming Growth Factor beta, Tumor Cells, Cultured, Two-Hybrid System Techniques, Yeasts
Nat. Cell Biol.
Date: Aug. 01, 2001
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