Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mineralocorticoid receptor (MR) is a member of the nuclear receptor superfamily. Pathological activation of the MR causes cardiac fibrosis and heart failure, but clinical use of MR antagonists is limited by the renal side effect of hyperkalemia. Coregulator proteins are known to be critical for nuclear receptor-mediated gene expression. Identification of coregulators, which mediate MR activity in a tissue-specific manner, may allow for the development of novel tissue-selective MR modulators that confer cardiac protection without adverse renal effects. Our earlier studies identified a consensus motif among MR-interacting peptides, MPxLxxLL. Gem (nuclear organelle)-associated protein 4 (GEMIN4) is one of the proteins that contain this motif. Transient transfection experiments in HEK293 and H9c2 cells demonstrated that GEMIN4 repressed agonist-induced MR transactivation in a cell-specific manner. Furthermore, overexpression of GEMIN4 significantly decreased, while knockdown of GEMIN4 increased, the mRNA expression of specific endogenous MR target genes. A physical interaction between GEMIN4 and MR is suggested by their nuclear co-localization upon agonist treatment. These findings indicate that GEMIN4 functions as a novel coregulator of the MR.
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PMID:GEMIN4 functions as a coregulator of the mineralocorticoid receptor. 2555 24

Gem-associated protein 4 (GEMIN4) gene is a key regulator for the miRNA biogenesis processes. Recent studies have demonstrated that some single-nucleotide polymorphisms (SNPs) in GEMIN4 gene are associated with the risk of cancer, but the results are still controversial. Therefore, we conducted a meta-analysis to analyze the association between three major SNPs (rs2740348, rs7813, and rs3744741) in the GEMIN4 gene and the risk of cancer. Relevant articles were searched in Web of Science, PubMed, Cochrane Library, Chinese Wan Fang, and Chinese National Knowledge Infrastructure databases. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated to quantitatively estimate the association. Publication bias and sensitivity analyses were undertaken to evaluate the stability of the results. Overall, the pooled results showed that rs2740348 involving 3,604 cases and 3,770 controls was significantly associated with increased cancer risk (GG vs GC/CC: OR =1.16, 95% CI =1.05-1.29, P=0.004) and rs7813 involving 4,729 cases and 4,562 controls was also related to increased cancer risk (TT vs TC/CC: OR =1.12, 95% CI =1.03-1.22, P=0.009). However, there was no significant association between rs3744741 and cancer risk under overall genetic models. In conclusion, our study has demonstrated that rs2740348 and rs7813 are associated with increased risk of cancer, and they may be new biomarkers for predicting cancer risk.
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PMID:Association of GEMIN4 gene polymorphism and the risk of cancer: a meta-analysis. 2913 79