EXPRESSION AND POST-TRANSLATIONAL MODIFICATION OF HUMAN 4-HYDROXY-PHENYLPYRUVATE DIOXYGENASE
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EXPRESSION AND POST-TRANSLATIONAL MODIFICATION OF HUMAN 4-HYDROXY-PHENYLPYRUVATE DIOXYGENASE. / Aarenstrup, Lene; Falch, Anne-Marie; Jakobsen, Kirsten K.; Neve, Søren; Henriksen, Linda Ø.; Tommerup, Niels; Leffers, Henrik; Kristiansen, Karsten.
I: Cell Biology International, Bind 26, Nr. 7, 2002, s. 615-625.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - EXPRESSION AND POST-TRANSLATIONAL MODIFICATION OF HUMAN 4-HYDROXY-PHENYLPYRUVATE DIOXYGENASE
AU - Aarenstrup, Lene
AU - Falch, Anne-Marie
AU - Jakobsen, Kirsten K.
AU - Neve, Søren
AU - Henriksen, Linda Ø.
AU - Tommerup, Niels
AU - Leffers, Henrik
AU - Kristiansen, Karsten
N1 - Author Keywords: chromosomal localization; footprinting; phosphorylation; 2D gel-electrophoresis; tyrosinemia
PY - 2002
Y1 - 2002
N2 - 4-hydroxyphenylpyruvate dioxygenase (HPD) (EC 1.13.11.27) is a key enzyme involved in tyrosine catabolism. Congenital HPD deficiency is a rare, relatively benign condition known as hereditary type III tyrosinemia. The severe type I tyrosinemia, caused by a deficiency of fumarylacetoacetate hydrolase which functions downstream of HPD in the tyrosine degradation pathway, is often associated with decreased expression of HPD, and interestingly, inhibition of HPD activity seems to ameliorate the clinical symptoms of type I tyrosinemia. The HPD gene was previously mapped to the chromosomal region 12q24¿qter. In the present study high-resolution chromosome mapping localized the HPD gene to 12q24.31. DNase I footprinting, revealed that four regions of the HPD promoter were protected by rat liver nuclear proteins. Computer-assisted analyses suggested that these elements might bind Sp1/AP2, HNF4, HNF3/CREB, and C/EBP, respectively. In transient transfection experiments, the proximal 271 bp of the promoter conferred basal transcriptional activation in human Chang cells. Sequences in intron 1 were able to enhance the activity of this basal promoter. Finally, vaccinia virus-based expression provided evidence that HPD is subject to phosphorylation, and furthermore, allowed mapping of the HPD protein in the human keratinocyte 2D database.
AB - 4-hydroxyphenylpyruvate dioxygenase (HPD) (EC 1.13.11.27) is a key enzyme involved in tyrosine catabolism. Congenital HPD deficiency is a rare, relatively benign condition known as hereditary type III tyrosinemia. The severe type I tyrosinemia, caused by a deficiency of fumarylacetoacetate hydrolase which functions downstream of HPD in the tyrosine degradation pathway, is often associated with decreased expression of HPD, and interestingly, inhibition of HPD activity seems to ameliorate the clinical symptoms of type I tyrosinemia. The HPD gene was previously mapped to the chromosomal region 12q24¿qter. In the present study high-resolution chromosome mapping localized the HPD gene to 12q24.31. DNase I footprinting, revealed that four regions of the HPD promoter were protected by rat liver nuclear proteins. Computer-assisted analyses suggested that these elements might bind Sp1/AP2, HNF4, HNF3/CREB, and C/EBP, respectively. In transient transfection experiments, the proximal 271 bp of the promoter conferred basal transcriptional activation in human Chang cells. Sequences in intron 1 were able to enhance the activity of this basal promoter. Finally, vaccinia virus-based expression provided evidence that HPD is subject to phosphorylation, and furthermore, allowed mapping of the HPD protein in the human keratinocyte 2D database.
U2 - 10.1006/cbir.2002.0896
DO - 10.1006/cbir.2002.0896
M3 - Journal article
VL - 26
SP - 615
EP - 625
JO - Cell Biology International
JF - Cell Biology International
SN - 1065-6995
IS - 7
ER -
ID: 14640335