Daxx, a Novel Fas-binding Protein That Activates JNK and Apoptosis

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 1997 Jun 27

PMID 9215629

Citations 260

Authors

X Yang

R Khosravi-Far

H Y Chang

D Baltimore

Affiliations

Soon will be listed here.

Abstract

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.

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