Expression and regulation of vitamin D3upregulated protein 1 (VDUP1) is conserved in mammalian and insect brain
Autor: | Jacilyn Basle, Mark C. Levendusky, Richard E. Dearborn, Jeffrey M. Voigt, Solomon Chang, Neil V. Mandalaywala |
---|---|
Rok vydání: | 2009 |
Předmět: |
Blood Glucose
Nervous system Cell Cycle Proteins E-box Biology Conserved sequence Evolution Molecular Rats Sprague-Dawley Downregulation and upregulation Tumor Cells Cultured medicine Animals Drosophila Proteins Humans Promoter Regions Genetic Enhancer Transcription factor Gene Conserved Sequence Neurons Genetics Gene Expression Profiling General Neuroscience Brain DNA Glioma Immunohistochemistry Rats Up-Regulation medicine.anatomical_structure Larva Neuroglia Drosophila Carrier Proteins Energy Metabolism |
Zdroj: | The Journal of Comparative Neurology. 517:581-600 |
ISSN: | 1096-9861 0021-9967 |
DOI: | 10.1002/cne.22195 |
Popis: | Originally characterized as a cell-cycle inhibitor induced by vitamin D(3), the tumor suppressor vitamin-D(3) upregulated protein 1 (VDUP1) has increasingly been shown to play major physiological roles in cell differentiation and glucose metabolism. Here we show evolutionarily conserved expression patterns of VDUP1 in Drosophila and rat nervous systems, including subcellular localization--cytoplasmic enrichment in neurons and nuclear expression in glia. These anatomical correlates suggested conservation of VDUP1 regulation, which was investigated both functionally and through promoter studies. Characterization of orthologous vdup1 cis-regulatory regions identified evolutionarily conserved sequence blocks (CSBs) with similarities to neural enhancers, including basic helix-loop-helix (bHLH) transcription factor Neurogenin/Math/atonal and Mash/achaete-scute family members. E-boxes (CANNTG), the binding sites for bHLH proteins, were associated with these CSBs as well, including E-boxes known to mediate glucose-dependent upregulation of VDUP1 in nonneuronal cells. Hyperglycemia-induced upregulation of VDUP1 was observed in brain tumor cells and in the Drosophila nervous system, which resulted in developmental arrest. Taken together, these data demonstrate evolutionary conservation of VDUP1 regulation and function, and suggest an expanding role for VDUP1 in nervous system development. |
Databáze: | OpenAIRE |
Externí odkaz: |