Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.1.2.13 (aldolase)
 3,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aldolase C (EC 4.1.2.13) is a brain-specific aldolase isoform and a putative target of the transcription factor hypoxia-inducible factor (HIF)-1. We identified aldolase C as a candidate hypoxia-regulated gene in mouse lung epithelial (MLE) cells using differential display. We show that the message accumulates in a robust fashion when MLE cells are exposed to 1% oxygen and is inversely related to oxygen content. Induction in hypoxia is dependent on protein synthesis. We localized a hypoxia-responsive element (HRE) in the aldolase C promoter using a series of deletion and heterologous expression studies. The HRE overlaps with a region of the proximal aldolase C promoter that is also related to its brain-specific expression. The HRE contains an Arnt (HIF-1beta) and an HIF-1alpha site. We show that induction in hypoxia is dependent on the HIF-1 site and that HIF-1alpha protein is present, by gel-shift assay, within nuclear complexes of MLE cells in hypoxia. Aldolase C mRNA expression is developmentally regulated in the fetal lung, rapidly downregulated in the newborn lung at birth, and inducible in the adult lung when exposed to hypoxia. This pattern of regulation is not seen in the brain. This preservation of this HRE in the promoters of four other species suggests that aldolase C may function as a stress-response gene.
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PMID:Hypoxia results in an HIF-1-dependent induction of brain-specific aldolase C in lung epithelial cells. 1679 80

There is increasing evidence that glycolysis is involved in cancer progression. Aldolase is a glycolytic enzyme that catalyzes the reversible conversion of fructose-1,6-bisphosphate to glyceraldehyde-3-phosphate and dihydroxyacetone phosphate. Disruption of the aldolase genes also plays a role in the progression of multiple types of cancer. However, the underlying mechanism of the action of aldolases in colon cancer progression remains elusive. In this study, aldolase A expression was investigated and found to be upregulated along with human colon cancer progression and metastasis at both the mRNA and protein levels in human colon cancer tissues. In addition, silencing aldolase A suppressed colon cancer cell proliferation and invasion and inhibited the EMT phenotype. Aldolase A protein expression in colon cancer was related to tumor location, tumor clinical stage and survival. Kaplan-Meier analysis showed that high aldolase A protein expression was associated with an unfavorable outcome. Moreover, aldolase A affected the development of colon cancer not only by affecting the glucose metabolism but also by interacting with the HIF-1 and other EMT-related signaling pathways; silencing aldolase A resulted in the reduced activity of these signaling pathways. These results indicate that aldolase A has additional non-glycolytic functions in transcriptional EMT regulation and may therefore have potential as a therapeutic target or a biomarker for identifying patients at risk for poorer survival.
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PMID:Aldolase A overexpression is associated with poor prognosis and promotes tumor progression by the epithelial-mesenchymal transition in colon cancer. 2945 83