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- Title
Identification of the Functional Autophagy-Regulatory Domain in <italic>HCLS1</italic>-Associated Protein X-1 That Resists Against Oxidative Stress.
- Authors
Li, Ying-Lan; Cai, Wen-Feng; Wang, Lei; Liu, Guan-Sheng; Paul, Christian; Jiang, Lin; Wang, Boyu; Gao, Xiang; Wang, Yigang; Wu, Shi-Zheng
- Abstract
<italic>HCLS1</italic> Associated Protein X-1 (HAX1) promotes cell survival through attenuation of the damaged signals from endoplasmic reticulum and mitochondria, which are known as prominent intracellular compartments for the autophagic process under stress conditions. This study investigates whether autophagy can be upregulated in response to HAX1 overexpression and identifies the functional motif in HAX1 responsible for the autophagic induction. Autophagosome accumulation, mitochondrial membrane potential (Δψm), and apoptosis were assessed in HEK293 cells post transduction with full-length or truncated HAX1-encoding genes, while empty vector-transduced cells served as control. Upon the oxidative stress, the enhanced autophagy induction was observed in cells overexpressing HAX1, as well as HAX1 truncations that encode peptide segments ranging from amino acids 127–180 (AA127-180). This protective response was further supported by flow cytometry and Western Blot results, in which oxidative stress-induced Δψm dissipation and the programmed cell death were suppressed in HAX1-overexpressing cells, associated with reduced DNA fragmentation and decreased Caspase-9 cleavage. Interestingly, the HAX1-induced autophagy response was abrogated when AA127-180 was removed, compromising the antiapoptotic effects upon oxidative stress. Overall, these data indicate that autophagy induction is involved in HAX1-induced cell protective mechanism, and AA127-180 serves as the functional autophagy-regulatory domain of this antiapoptotic protein.
- Subjects
OXIDATIVE stress; AUTOPHAGY; ENDOPLASMIC reticulum; MITOCHONDRIA; PROTEINS
- Publication
DNA & Cell Biology, 2018, Vol 37, Issue 5, p432
- ISSN
1044-5498
- Publication type
Article
- DOI
10.1089/dna.2017.3873