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Expression and regulation of vitamin D 3 upregulated protein 1 (VDUP1) is conserved in mammalian and insect brain
Author(s) -
Levendusky Mark C.,
Basle Jacilyn,
Chang Solomon,
Mandalaywala Neil V.,
Voigt Jeffrey M.,
Dearborn Richard E.
Publication year - 2009
Publication title -
journal of comparative neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.855
H-Index - 209
eISSN - 1096-9861
pISSN - 0021-9967
DOI - 10.1002/cne.22195
Subject(s) - biology , downregulation and upregulation , transcription factor , subcellular localization , conserved sequence , microbiology and biotechnology , nuclear export signal , nervous system , regulation of gene expression , cytoplasm , genetics , gene , neuroscience , cell nucleus , peptide sequence
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. J. Comp. Neurol. 517:581–600, 2009. © 2009 Wiley‐Liss, Inc.