Apoptosis can be induced by certain cytokines including TNF and Fas ligand through binding to their respective death domain (DD) containing receptors, TNFR1 and Fas. Cell death signals can then be transduced by DD-containing adapter molecules and members of the caspase family. A novel DD-containing adapter molecule was recently cloned from mouse, human and monkey and designated Daxx. Daxx binds to the Fas DD and activates a FADD-independent death pathway that involves the stress activated c-Jun NH2-terminal kinase (JNK). Daxx activates the JNK kinase kinase ASK1 that is also known as MAPKKK5. FADD and Daxx activate two independent pathways downstream of Fas. Daxx mRNA is widely expressed in fetal and adult tissues with the highest amounts being found in the testis.
