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

Article Details

Citation

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

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

Nat Cell Biol. 2001 Aug;3(8):708-14.

PubMed ID
11483955 [ View in PubMed
]
Abstract

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.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
TGF-beta receptor type-2P37173Details