Daxx, a novel Fas-binding protein that activates JNK and apoptosis.
The Fas cell surface receptor induces apoptosis upon receptor oligomerization. We have identified a novel signaling protein, termed Daxx, that binds specifically to the Fas death domain. Overexpression of Daxx enhances Fas-mediated apoptosis and activates the Jun N-terminal kinase (JNK) pathway. A C-terminal portion of Daxx interacts with the Fas death domain, while a different region activates both JNK and apoptosis. The Fas-binding domain of Daxx is a dominant-negative inhibitor of both Fas-induced apoptosis and JNK activation, while the FADD death domain partially inhibits death but not JNK activation. The Daxx apoptotic pathway is sensitive to both Bcl-2 and dominant-negative JNK pathway components and acts cooperatively with the FADD pathway. Thus, Daxx and FADD define two distinct apoptotic pathways downstream of Fas.
Pubmed ID: 9215629 RIS Download
Adaptor Proteins, Signal Transducing | Amino Acid Sequence | Animals | Antigens, CD95 | Apoptosis | Arabidopsis Proteins | Blotting, Northern | Calcium-Calmodulin-Dependent Protein Kinases | Carrier Proteins | Cloning, Molecular | DNA, Complementary | Fatty Acid Desaturases | Gene Deletion | HeLa Cells | Humans | Intracellular Signaling Peptides and Proteins | JNK Mitogen-Activated Protein Kinases | Mice | Mitogen-Activated Protein Kinases | Molecular Sequence Data | Mutagenesis | Nuclear Proteins | Plant Proteins | Proto-Oncogene Proteins c-bcl-2 | RNA, Messenger | Receptors, Cell Surface | Signal Transduction | Yeasts