Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pleomorphic adenomas gene-like 2 (PLAGL2) protein containing seven C(2)H(2) zinc finger motifs exhibits DNA binding and transcriptional activation activity and is expressed in response to hypoxia or iron deficiency. To identify the target genes of PLAGL2, we transfected mouse PLAGL2 cDNA into Balb/c3T3 fibroblasts and neuroblastoma Neuro2a cells. Both cells were induced to undergo apoptosis by the expression of PLAGL2 as judged by assays of TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP nick end-labeling), DNA fragmentation, propidium iodide staining, and the binding of annexin V to the cell surface. The treatment of the cells with an iron chelator, desferrioxamine, resulted in the induction of apoptosis with a concomitant accumulation of PLAGL2 in the nucleus. The expression of PLAGL2 in Balb/c3T3 cells led to the mRNA expression of a proapoptotic factor, Nip3, which can dimerize with Bcl-2. Nip3 mRNA was also induced in desferrioxamine-treated cells. Furthermore, the Nip3 promoter containing a hypoxia-responsive element was activated by PLAGL2, independent of hypoxia-inducible factor-1 (HIF-1). The transfection of antisense oligonucleotide to mouse Nip3 mRNA into PLAGL2-expressing cells led to a decrease in apoptotic cells compared with sense oligonucleotide-transfected cells. Despite the activation of DNA-HIF-1 binding activity under hypoxic conditions, neither an accumulation of HIF-1 alpha nor the activation of HIF-1 was observed following the expression of PLAGL2. These results indicate that PLAGL2 is located downstream of HIF-1 and suggest that PLAGL2 functions as a tumor suppressor in association with HIF-1.
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PMID:A zinc-finger protein, PLAGL2, induces the expression of a proapoptotic protein Nip3, leading to cellular apoptosis. 1183 86

The transcription factor Sox11 is expressed at high levels in developing sensory neurons and injured adult neurons but little is known about its transcriptional targets and function. In this study we examined the role of Sox11 using Neuro2a neuroblastoma cells and cultured mouse dorsal root ganglia (DRG) neurons. Results show Sox11 has an essential role in regulation of neuron survival and neurite outgrowth in Neuro2a cells and primary sensory neurons. Neuro2a cells increase expression of Sox11 as they differentiate in culture. Following addition of 20 microM retinoic acid (RA), a stimulus for differentiation that enhances neurite growth and differentiation, Sox11 level rises. RNAi-mediated knockdown of Sox11 in RA-differentiated Neuro2a cells caused a decrease in neurite growth and an increase in the percent of apoptotic cells. RNA expression analysis showed that Sox11 knockdown modulated the level of mRNAs encoding several genes related to cell survival and death. Further validation in the Neuro2a model showed Sox11 knockdown increased expression of the pro-apoptotic gene BNIP3 (BclII interacting protein 1 NIP3) and decreased expression of the anti-apoptotic gene TANK (TNF receptor-associated factor family member-associated NFkappaB activator). Cultured primary DRG neurons also express Sox11 and treatment with Sox11 small interfering RNA (siRNA) caused a significant decrease in neurite growth and branching and a decrease in mRNA encoding actin-related protein complex 3 (Arpc3), an actin organizing protein that may be involved in axon growth. The percent of apoptotic neurons also increased in cultures of DRG neurons treated with Sox11 siRNA. Similar to Neuro2a cells, a decrease in TANK gene expression occurred, suggesting at least some overlap in Sox11 transcriptional targets in Neuro2a and DRG neurons. These data are consistent with a central role for Sox11 in regulating events that promote neurite growth and neuron survival.
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PMID:SRY-box containing gene 11 (Sox11) transcription factor is required for neuron survival and neurite growth. 1705 61