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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.

Pubmed ID: 11483955

Authors

  • Perlman R
  • Schiemann WP
  • Brooks MW
  • Lodish HF
  • Weinberg RA

Journal

Nature cell biology

Publication Data

August 2, 2001

Associated Grants

None

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