Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P30044 (antioxidant enzyme)
8,037 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Respiratory syncytial virus (RSV) is the most important cause of viral acute respiratory tract infections and hospitalizations in children, for which no vaccine or specific treatments are available. RSV causes airway mucosa inflammation and cellular oxidative damage by triggering production of reactive oxygen species and by inhibiting at the same time expression of antioxidant enzymes, via degradation of the transcription factor NF-E2-related factor 2 (NRF2). RSV infection induces NRF2 deacetylation, ubiquitination, and degradation through a proteasome-dependent pathway. Although degradation via KEAP1 is the most common mechanism, silencing KEAP1 expression did not rescue NRF2 levels during RSV infection. We found that RSV-induced NRF2 degradation occurs in an SUMO-specific E3 ubiquitin ligase - RING finger protein 4 (RNF4)-dependent manner. NRF2 is progressively SUMOylated in RSV infection and either blocking SUMOylation or silencing RNF4 expression rescued both NRF2 nuclear levels and transcriptional activity. RNF4 associates with promyelocytic leukemia - nuclear bodies (PML-NBs). RSV infection induces the expression of PML and PML-NBs formation in an interferon (INF)-dependent manner and also induces NRF2 - PMN-NBs association. Inhibition of PML-NB formation by blocking IFN pathway or silencing PML expression resulted in a significant reduction of RSV-associated NRF2 degradation and increased antioxidant enzyme expression, identifying the RNF4-PML pathway as a key regulator of antioxidant defenses in the course of viral infection.
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PMID:Respiratory syncytial virus induces NRF2 degradation through a promyelocytic leukemia protein - ring finger protein 4 dependent pathway. 2910 45

Post-translational modification of cellular proteins by sumoylation plays a vital role in stress responses of plants. However, the mechanisms underlying the sumoylation's involvement in stress responses in crop species remain largely unknown. Herein, a maize class-I SUMO conjugating enzyme gene (ZmSCE1d) was identified, whose expression was upregulated upon drought stress. Over-expression of ZmSCE1d in transgenic Arabidopsis plants increased SUMO conjugates and improved drought tolerance. The ZmSCE1d-transgenic plants showed higher antioxidant enzyme activities, but lower reactive oxygen species and lipid peroxidation upon drought stress. Furthermore, transcripts of several drought-responsive genes were significantly elevated, as revealed by qPCR in the transgenic lines. Taken together, these data have demonstrated that ZmSCE1d overexpression improved drought tolerance likely by regulating sumoylation levels, antioxidant capability, and drought-responsive gene expression in transgenic plants. This study may facilitate our understanding of the mechanisms underlying SCE-mediated sumoylation under drought stress and accelerate genetic improvement of crop plants tolerant to drought stress by manipulating the SUMO system.
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PMID:The Maize Class-I SUMO Conjugating Enzyme ZmSCE1d Is Involved in Drought Stress Response. 3186 56