Role of the von Hippel-Lindau tumor suppressor protein during neuronal differentiation.
The von Hippel-Lindau (VHL) tumor suppressor protein down-regulates transcription by transcriptional elongation enhanced by antagonizing elongin B and C. Transcriptional regulation is an important control mechanism for embryogenesis and tumorigenesis. The VHL gene and protein are expressed in neuronal cells of the fetal and adult brain. However, the role of the VHL gene in the central nervous system (CNS) has not been elucidated. The VHL gene might modify the expression of various genes during embryogenesis and tumorigenesis in CNS. We investigated the role of the VHL gene in CNS development using rodent CNS progenitor cells. Here we show that expression of the VHL protein is correlated with neuronal differentiation but not with glial differentiation in CNS progenitor cells, and we also show that VHL gene transduction induces neuronal differentiation. In addition, a VHL mRNA antisense oligonucleotide inhibits differentiation of CNS progenitor cells and up-regulates their cell cycle. In conclusion, the VHL gene plays an essential role in neuronal differentiation as well as transcription.
Kanno
H
H
Division of Neurosurgery, Veterans Administration San Diego Healthcare System, University of California San Diego, 92161, USA. kanno@med.yokohama-cu.ac.jp
Saljooque
F
F
Yamamoto
I
I
Hattori
S
S
Yao
M
M
Shuin
T
T
U
H S
HS
D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation; D015536:Down-Regulation; D004622:Embryo, Mammalian / Q000502:physiology; D004815:Epidermal Growth Factor / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000378:metabolism; D005786:Gene Expression Regulation; D016147:Genes, Tumor Suppressor / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry; D007381:Intermediate Filament Proteins / Q000378:metabolism; D008025:Ligases; D018613:Microscopy, Confocal; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins; D064231:Nestin; D009474:Neurons / Q000166:cytology* / Q000502:physiology*; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic; D014161:Transduction, Genetic; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein
D005904:Glial Fibrillary Acidic Protein; D007381:Intermediate Filament Proteins; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; C577486:Nes protein, rat; D064231:Nestin; D016376:Oligonucleotides, Antisense; D011506:Proteins; D025521:Tumor Suppressor Proteins; D005346:Fibroblast Growth Factors; D004815:Epidermal Growth Factor; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D008025:Ligases