| RRC ID |
28656
|
| 著者 |
Urano Y, Iiduka M, Sugiyama A, Akiyama H, Uzawa K, Matsumoto G, Kawasaki Y, Tashiro F.
|
| タイトル |
Involvement of the mouse Prp19 gene in neuronal/astroglial cell fate decisions.
|
| ジャーナル |
J Biol Chem
|
| Abstract |
The molecular mechanisms involved in neuronal/astroglial cell fate decisions during the development of the mammalian central nervous system are poorly understood. Here, we report that PRP19beta, a splice variant of mouse PRP19alpha corresponding to the yeast PRP19 protein, can function as a neuron-astroglial switch during the retinoic acid-primed neural differentiation of P19 cells. The beta-variant possesses an additional 19 amino acid residues in-frame in the N-terminal region of the alpha-variant. The forced expression of the alpha-variant RNA caused the down-regulation of oct-3/4 and nanog mRNA expression during the 12-48 h of the late-early stages of neural differentiation and was sufficient to convert P19 cells into neurons (but not glial cells) when the cells were cultured in aggregated form without retinoic acid. In contrast, the forced expression of the beta-variant RNA suppressed neuronal differentiation and conversely stimulated astroglial cell differentiation in retinoic acid-primed P19 cells. Based on yeast two-hybrid screening, cyclophilin A was identified as a specific binding partner of the beta-variant. Luciferase reporter assay mediated by the oct-3/4 promoter revealed that cyclophilin A could act as a transcriptional activator and that its activity was suppressed by the beta-variant, suggesting that cyclophilin A takes part in the induction of oct-3/4 gene expression, which might lead to neuroectodermal otx2 expression within 12 h of the immediate-early stages of retinoic acid-primed neural differentiation. These results show that the alpha-variant gene plays a pivotal role in neural differentiation and that the beta-variant participates in neuronal/astroglial cell fate decisions.
|
| 巻・号 |
281(11)
|
| ページ |
7498-514
|
| 公開日 |
2006-3-17
|
| DOI |
10.1074/jbc.M510881200
|
| PII |
S0021-9258(19)35375-X
|
| PMID |
16352598
|
| MeSH |
Alternative Splicing
Amino Acid Sequence
Animals
Base Sequence
Blotting, Northern
Carrier Proteins / physiology*
Cell Differentiation
Cell Line
Cell Lineage
Cells, Cultured
Chromatin Immunoprecipitation
Chromatography, Gel
Cloning, Molecular
Cyclophilin A / chemistry
DNA Primers / chemistry
DNA Repair Enzymes
DNA, Complementary / metabolism
Dose-Response Relationship, Drug
Down-Regulation
Genetic Vectors
Green Fluorescent Proteins / metabolism
Immunoprecipitation
Luciferases / metabolism
Mice
Mice, Inbred ICR
Models, Biological
Molecular Sequence Data
Neuroglia / metabolism*
Neurons / metabolism
Nuclear Proteins
Oligonucleotides / chemistry
Promoter Regions, Genetic
Protein Binding
Protein Structure, Tertiary
RNA / chemistry
RNA / metabolism
RNA Splicing Factors
RNA, Messenger / metabolism
Rats
Reverse Transcriptase Polymerase Chain Reaction
Sequence Homology, Amino Acid
Spliceosomes / metabolism
Time Factors
Tissue Distribution
Two-Hybrid System Techniques
|
| IF |
4.238
|
| 引用数 |
25
|
|
WOS 分野
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| リソース情報 |
| 遺伝子材料 |
pFlag-CMV2/PRP19beta (RDB07945) |
