. Interaction of DJ-1 with Daxx inhibits apoptosis signal-regulating kinase 1 activity and cell death. Proc Natl Acad Sci U S A. 2005 Jul 5;102(27):9691-6. PubMed.


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  1. The observation that DJ-1 is capable of protecting cells against oxidant-induced cell death has been confirmed in several laboratories without a very clear mechanism emerging for how this would happen. Showing that simple scavenging of radicals is not likely to account for neuroprotection, as Junn et al. do in this study, is important. It has never seemed likely to me that a protein like DJ-1 provides very much antioxidant capacity in a cell full of low molecular weight thiols. Junn et al. show that the previous data from Ariga showing that DJ-1 decreases intracellular hydrogen peroxide is correct, but argue that there must be another protective mechanism as the decrease in peroxide levels is smaller than the percentile suppression of cell death. They have gone on to show that DJ-1 interacts with, amongst other proteins, Daxx, and suggest that this mechanism accounts for neuroprotection via an ASK1 pathway. Although ASK1 is named for its effects on apoptosis, I wonder if DJ-1’s protective ability is on apoptosis per se or whether it is broader than that. Yokota et al. have shown that DJ-1 is not a suppressor of staurosporine-induced apoptosis. Perhaps DJ-1 requires activation, such as by oxidation, before it can protect cells. Also, at least in my lab, MPP+ doesn’t produce a strict apoptotic cell death even though DJ-1 is protective. It is interesting that although Daxx and ASK1 usually work through classical apoptosis pathways (Song and Lee, 2004), ASK1 can also activate cell death in a fashion that doesn’t include many of the hallmarks of nuclear apoptosis (Zhang et al., 2004).


    . Down regulation of DJ-1 enhances cell death by oxidative stress, ER stress, and proteasome inhibition. Biochem Biophys Res Commun. 2003 Dec 26;312(4):1342-8. PubMed.

    . Daxx deletion mutant (amino acids 501-625)-induced apoptosis occurs through the JNK/p38-Bax-dependent mitochondrial pathway. J Cell Biochem. 2004 Aug 15;92(6):1257-70. PubMed.

    . Thioredoxin-2 inhibits mitochondria-located ASK1-mediated apoptosis in a JNK-independent manner. Circ Res. 2004 Jun 11;94(11):1483-91. PubMed.

    View all comments by Mark Cookson
  2. The recent finding from Junn and the Mouradian group on DJ-1 interacting with Daxx is very interesting. First, by using the two hybridization system, Junn et al. found that DJ-1 can bind Daxx, which is a component of the Fas death receptor signal transduction pathway. Moreover, they found that DJ-1 protects cells not only from free radicals, but also against Daxx/ASK-1-induced cell death. This study provides important evidence to elucidate of functional mechanisms of DJ-1 antioxidation. These studies are done in vitro. It will be interesting to examine whether the functional relationship between DJ-1 and Daxx will retain the same pattern in vivo. Furthermore, more studies need to investigate why the DJ-1 protective signal transduction pathway mainly occurs in the dopaminergic neuronal system, since DJ-1 or Daxx are widely expressed not only in the brain, but also in the peripheral nervous system, and not only in the dopamine system, but also in many other systems in the brain. Lastly, one important function of DJ-1 is considered to depend on macrocomplexes in normal brains, since once DJ-1 becomes a monomer or oligomer, it may lose its protective function. However, all of the studies Junn et al. reported were conducted in vitro and DJ-1 seems to interact with other molecules, i.e., Daxx as a monomer. DJ-1 functions and roles in neuroprotection need further exploration, discussion, and interpretation.

    View all comments by Yong Shen

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  1. DJ-1 Dances with Daxx to Keep Neurons Spry