Редактирование: HACE1 (раздел)

==Publications==

{{medline-entry
|title=[[HACE1]] reduces oxidative stress and mutant Huntingtin toxicity by promoting the NRF2 response.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/24516159
|abstract=Oxidative stress plays a key role in late onset diseases including cancer and neurodegenerative diseases such as Huntington disease. Therefore, uncovering regulators of the antioxidant stress responses is important for understanding the course of these diseases. Indeed, the nuclear factor erythroid 2-related factor 2 (NRF2), a master regulator of the cellular antioxidative stress response, is deregulated in both cancer and neurodegeneration. Similar to NRF2, the tumor suppressor Homologous to the E6-AP Carboxyl Terminus (HECT) domain and Ankyrin repeat containing E3 ubiquitin-protein ligase 1 ([[HACE1]]) plays a protective role against stress-induced tumorigenesis in mice, but its roles in the antioxidative stress response or its involvement in neurodegeneration have not been investigated. To this end we examined Hace1 WT and KO mice and found that Hace1 KO animals exhibited increased oxidative stress in brain and that the antioxidative stress response was impaired. Moreover, [[HACE1]] was found to be essential for optimal NRF2 activation in cells challenged with oxidative stress, as [[HACE1]] depletion resulted in reduced NRF2 activity, stability, and protein synthesis, leading to lower tolerance against oxidative stress triggers. Strikingly, we found a reduction of [[HACE1]] levels in the striatum of Huntington disease patients, implicating [[HACE1]] in the pathology of Huntington disease. Moreover, ectopic expression of [[HACE1]] in striatal neuronal progenitor cells provided protection against mutant Huntingtin-induced redox imbalance and hypersensitivity to oxidative stress, by augmenting NRF2 functions. These findings reveal that the tumor suppressor [[HACE1]] plays a role in the NRF2 antioxidative stress response pathway and in neurodegeneration. 
|mesh-terms=* Animals
* Blotting, Western
* Cell Fractionation
* Corpus Striatum
* DNA Primers
* Fluorescent Antibody Technique
* HEK293 Cells
* Humans
* Huntingtin Protein
* Huntington Disease
* Mice
* NF-E2-Related Factor 2
* Nerve Tissue Proteins
* Oxidative Stress
* Reactive Oxygen Species
* Real-Time Polymerase Chain Reaction
* Ubiquitin-Protein Ligases
|keywords=* ROS
* aging
* glutathione
* transcription factor
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3939919
}}