PMID- 17394463
OWN - NLM
STAT- MEDLINE
DCOM- 20070529
LR  - 20231213
IS  - 0022-3042 (Print)
IS  - 0022-3042 (Linking)
VI  - 101
IP  - 1
DP  - 2007 Apr
TI  - Regulation of GTP cyclohydrolase I expression by orphan receptor Nurr1 in cell 
      culture and in vivo.
PG  - 142-50
AB  - Nurr1 is an orphan nuclear transcription factor essential for the terminal 
      differentiation of dopamine (DA) neurons in the ventral midbrain (VM). To 
      identify the Nurr1-target genes, we carried out microarray and quantitative 
      real-time PCR analyses of Nurr1 null and wild-type mice in VM at embryonic day 
      (E) 12.5 and shortly after birth (P0). In addition to the absence of mRNAs of DA 
      synthesizing enzymes, the guanosine 5'-triphosphate (GTP) cyclohydrolase I 
      (GTPCH) was also substantially reduced in the VM of Nurr1-null mice. GTPCH is the 
      first enzyme in the synthesis pathway of tetrahydrobiopterin (BH4), an essential 
      cofactor for tyrosine hydroxylase in DA synthesis. In the mouse, Nurr1 and GTPCH 
      mRNA were first detected at E10.5, and GTPCH transcription paralleled that of 
      Nurr1. Small interfering RNA targeted against Nurr1 decreases GTPCH expression in 
      MC3T3-E1 osteoblasts in cell culture. Cotransfection of Nurr1 and the 
      GTPCH-luciferase (luc) reporter increased the luc activity by about threefold in 
      N2A cells. Additional analysis using 5'-deletions and mutants revealed that Nurr1 
      activates GTPCH transcription indirectly through the proximal promoter region, in 
      the absence of the nerve growth factor-induced clone B (NGFI-B) responsive 
      element-like sites, similarly, as recently reported for DA transporter regulation 
      by Nurr1.
FAU - Gil, Minchan
AU  - Gil M
AD  - Genetics and Biochemistry Branch, National Institute of Diabetes and Digestive 
      and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, 
      USA.
FAU - McKinney, Cushla
AU  - McKinney C
FAU - Lee, Mi Kyeong
AU  - Lee MK
FAU - Eells, Jeffrey B
AU  - Eells JB
FAU - Phyillaier, Marcia A
AU  - Phyillaier MA
FAU - Nikodem, Vera M
AU  - Nikodem VM
LA  - eng
GR  - Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Nr4a1 protein, mouse)
RN  - 0 (Nr4a2 protein, mouse)
RN  - 0 (Nuclear Receptor Subfamily 4, Group A, Member 1)
RN  - 0 (Nuclear Receptor Subfamily 4, Group A, Member 2)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 0 (Receptors, Steroid)
RN  - 0 (Transcription Factors)
RN  - 0 (Biopterins)
RN  - EC 3.5.4.16 (GTP Cyclohydrolase)
RN  - EGX657432I (sapropterin)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - Animals
MH  - Biopterins/analogs & derivatives/biosynthesis
MH  - Cells, Cultured
MH  - DNA-Binding Proteins/genetics/*metabolism
MH  - Dopamine/biosynthesis
MH  - Down-Regulation/genetics
MH  - Enzyme Activation/genetics
MH  - Female
MH  - GTP Cyclohydrolase/genetics/*metabolism
MH  - Gene Expression Regulation, Enzymologic/*physiology
MH  - Genes, Reporter/genetics
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Mutation/genetics
MH  - Nuclear Receptor Subfamily 4, Group A, Member 1
MH  - Nuclear Receptor Subfamily 4, Group A, Member 2
MH  - Oligonucleotide Array Sequence Analysis
MH  - Promoter Regions, Genetic/genetics
MH  - RNA, Messenger/analysis/metabolism
MH  - RNA, Small Interfering
MH  - Receptors, Cytoplasmic and Nuclear/metabolism
MH  - Receptors, Steroid/metabolism
MH  - Transcription Factors/genetics/*metabolism
MH  - Transcriptional Activation/physiology
MH  - Tumor Cells, Cultured
EDAT- 2007/03/31 09:00
MHDA- 2007/05/30 09:00
CRDT- 2007/03/31 09:00
PHST- 2007/03/31 09:00 [pubmed]
PHST- 2007/05/30 09:00 [medline]
PHST- 2007/03/31 09:00 [entrez]
AID - JNC4356 [pii]
AID - 10.1111/j.1471-4159.2006.04356.x [doi]
PST - ppublish
SO  - J Neurochem. 2007 Apr;101(1):142-50. doi: 10.1111/j.1471-4159.2006.04356.x.