Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The transcriptional activation of CHOP (C/EBP-homologous protein) by amino acid deprivation involves ATF2 and ATF4 binding at the amino acid response element within the promoter. In this report, we investigate the role of JDP2 (Jun Dimerization Protein 2) in the amino acid control of CHOP transcription following amino acid starvation. Our results show that JDP2 binds to the CHOP AARE in unstimulated cells and that its binding decreases following amino acid starvation. We demonstrate that JDP2 acts as a repressor and suggest that it could be functionally associated with HDAC3 to inhibit CHOP transcription.
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PMID:Role of the repressor JDP2 in the amino acid-regulated transcription of CHOP. 1839 63

Genetic ablation of Iron Regulatory Protein 2 (Irp2, Ireb2), which post-transcriptionally regulates iron metabolism genes, causes a gait disorder in mice that progresses to hind-limb paralysis. Here we have demonstrated that misregulation of iron metabolism from loss of Irp2 causes lower motor neuronal degeneration with significant spinal cord axonopathy. Mitochondria in the lumbar spinal cord showed significantly decreased Complex I and II activities, and abnormal morphology. Lower motor neurons appeared to be the most adversely affected neurons, and we show that functional iron starvation due to misregulation of iron import and storage proteins, including transferrin receptor 1 and ferritin, may have a causal role in disease. We demonstrated that two therapeutic approaches were beneficial for motor neuron survival. First, we activated a homologous protein, IRP1, by oral Tempol treatment and found that axons were partially spared from degeneration. Secondly, we genetically decreased expression of the iron storage protein, ferritin, to diminish functional iron starvation. These data suggest that functional iron deficiency may constitute a previously unrecognized molecular basis for degeneration of motor neurons in mice.
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PMID:Iron insufficiency compromises motor neurons and their mitochondrial function in Irp2-null mice. 2200 90