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)

Transcription factors (TFs) play critical roles in mediating defense of plants to abiotic stresses through regulating downstream defensive genes. In this study, a wheat C2H2-ZFP (zinc finger protein) type TF gene designated as TaZAT8 was functionally characterized in mediating tolerance to the inorganic phosphate (Pi)-starvation stress. TaZAT8 bears conserved motifs harboring in the C2H2-ZFP type counterparts across vascular plant species. The expression of TaZAT8 was shown to be induced in roots upon Pi deprivation, with a Pi concentration- and temporal-dependent manner. Overexpression of TaZAT8 in tobacco conferred plants improved tolerance to Pi deprivation; the transgenic lines exhibited enlarged phenotype and elevated biomass and phosphorus (P) accumulation relative to wild-type (WT) after Pi-starvation treatment. NtPT1 and NtPT2, the tobacco phosphate transporter (PT) genes, showed increased transcripts in the Pi-deprived transgenic lines, indicative of their transcriptional regulation by TaZAT8. Overexpression analysis of these PT genes validated their function in mediating Pi acquisition under the Pi deprivation conditions. Additionally, the TaZAT8-overexpressing lines also behaved enhanced antioxidant enzyme (AE) activities and enlarged root system architecture (RSA) with respect to WT. Evaluation of the transcript abundance of tobacco genes encoding AE and PIN proteins, including NtMnSOD1, NtSOD1, NtPOD1;2, NtPOD1;5, NtPOD1;6, and NtPOD1;9, and NtPIN1 and NtPIN4 are upregulated in the TaZAT8-overexpressing lines. Overexpression of NtPIN1 and NtPIN4 conferred plants to enlarged RSA and elevated biomass under the Pi-starvation stress conditions. Our investigation provides insights into plant adaptation to the Pi-starvation stress mediated by distinct ZFP TFs through modulation of Pi acquisition and cellular ROS detoxicity.
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PMID:TaZAT8, a C2H2-ZFP type transcription factor gene in wheat, plays critical roles in mediating tolerance to Pi deprivation through regulating P acquisition, ROS homeostasis and root system establishment. 2719 19

The incidence of prostate cancer (PCa) is increasing, and it is currently the second most frequent cause of death by cancer in men. Despite advancements in cancer therapies, new therapeutic approaches are still needed for treatment-refractory advanced metastatic PCa. Cross-species analysis presents a robust strategy for the discovery of new potential therapeutic targets. This strategy involves the integration of genomic data from genetically engineered mouse models (GEMMs) and human PCa datasets. Considering the role of antioxidant pathways in tumor initiation and progression, we searched oxidative stress-related genes for a potential therapeutic target for PCa. First, we analyzed RNA-sequencing data from Pb-Cre4; Ptenf/f mice and discovered an increase in sulfiredoxin (Srxn1) mRNA expression in high-grade prostatic intraepithelial neoplasia (PIN), well-differentiated adenocarcinoma (medium-stage tumors), and poor-differentiated adenocarcinoma (advanced-stage prostate tumors). The increase of SRXN1 protein expression was confirmed by immunohistochemistry in mouse prostate tumor paraffin samples. Analyses of human databases and prostate tissue microarrays demonstrated that SRXN1 is overexpressed in a subset of high-grade prostate tumors and correlates with aggressive PCa with worse prognosis and decreased survival. Analyses in vitro showed that SRXN1 expression is also higher in most PCa cell lines compared to normal cell lines. Furthermore, siRNA-mediated downregulation of SRXN1 led to decreased viability of PCa cells LNCaP. In conclusion, we identified the antioxidant enzyme SRXN1 as a potential therapeutic target for PCa. Our results suggest that the use of specific SRXN1 inhibitors may be an effective strategy for the adjuvant treatment of castration-resistant PCa with SRXN1 overexpression.
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PMID:Sulfiredoxin as a Potential Therapeutic Target for Advanced and Metastatic Prostate Cancer. 3241 20