English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

DJ-1 , a Parkinson's disease (PD)–associated gene, has been shown to protect against oxidative stress in  Drosophila . However, the molecular mechanism underlying oxidative stress-induced phenotypes, including apoptosis, locomotive defects, and lethality, in  DJ-1 -deficient flies is not fully understood. Here we showed that  Daxx-like protein  ( DLP ), a  Drosophila  homologue of the mammalian  Death domain-associated protein  ( Daxx ), was upregulated under oxidative stress conditions in the loss-of-function mutants of  Drosophila DJ-1β , a  Drosophila  homologue of  DJ-1 .  DLP  overexpression induced apoptosis via the c-Jun N-terminal kinase (JNK)/ Drosophila  forkhead box subgroup O (dFOXO) pathway, whereas loss of  DLP  increased resistance to oxidative stress and UV irradiation. Moreover, the oxidative stress-induced phenotypes of  DJ-1β  mutants were dramatically rescued by  DLP  deficiency, suggesting that enhanced expression of  DLP  contributes to the  DJ-1β  mutant phenotypes. Interestingly, we found that dFOXO was required for the increase in  DLP  expression in  DJ-1β  mutants and that dFOXO activity was increased in the heads of  DJ-1β  mutants. In addition, subcellular localization of DLP appeared to be influenced by  DJ-1  expression so that cytosolic DLP was increased in  DJ-1β  mutants. Similarly, in mammalian cells, Daxx translocation from the nucleus to the cytosol was suppressed by overexpressed  DJ-1β  under oxidative stress conditions; and, furthermore, targeted expression of  DJ-1β  to mitochondria efficiently inhibited the Daxx translocation. Taken together, our findings demonstrate that DJ-1β protects flies against oxidative stress- and UV-induced apoptosis by regulating the subcellular localization and gene expression of DLP, thus implying that Daxx-induced apoptosis is involved in the pathogenesis of  DJ-1 -associated PD.

Drosophila DJ-1 Decreases Neural Sensitivity to Stress by Negatively Regulating Daxx-Like Protein through dFOXO