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Anti-apoptotic quinolinate phosphoribosyltransferase (QPRT) is a target gene of Wilms' tumor gene 1 (WT1) protein in leukemic cells

Ullmark, Tove LU ; Montano, Giorgia LU ; Järvstråt, Linnea LU ; Jernmark Nilsson, Helena LU ; Håkansson, Erik; Drott, Kristina LU ; Nilsson, Björn LU ; Vidovic, Karina LU and Gullberg, Urban LU (2017) In Biochemical and Biophysical Research Communications 482(4). p.802-807
Abstract

Wilms' tumor gene 1 (WT1) is a zinc finger transcription factor that has been implicated as an oncogene in leukemia and several other malignancies. When investigating possible gene expression network partners of . WT1 in a large acute myeloid leukemia (AML) patient cohort, one of the genes with the highest correlation to . WT1 was quinolinate phosphoribosyltransferase (QPRT), a key enzyme in the . de novo nicotinamide adenine dinucleotide (NAD+) synthesis pathway. To investigate the possible relationship between . WT1 and . QPRT, we overexpressed . WT1 in hematopoietic progenitor cells and cell lines, resulting in an increase of . QPRT expression. WT1 knock-down gave a corresponding decrease in . QPRT gene and protein expression.... (More)

Wilms' tumor gene 1 (WT1) is a zinc finger transcription factor that has been implicated as an oncogene in leukemia and several other malignancies. When investigating possible gene expression network partners of . WT1 in a large acute myeloid leukemia (AML) patient cohort, one of the genes with the highest correlation to . WT1 was quinolinate phosphoribosyltransferase (QPRT), a key enzyme in the . de novo nicotinamide adenine dinucleotide (NAD+) synthesis pathway. To investigate the possible relationship between . WT1 and . QPRT, we overexpressed . WT1 in hematopoietic progenitor cells and cell lines, resulting in an increase of . QPRT expression. WT1 knock-down gave a corresponding decrease in . QPRT gene and protein expression. Chromatin-immunoprecipitation revealed WT1 binding to a conserved site in the first intron of the . QPRT gene. Upon overexpression in leukemic K562 cells, QPRT conferred partial resistance to the anti-leukemic drug imatinib, indicating possible anti-apoptotic functions, consistent with previous reports on glioma cells. Interestingly, the rescue effect of QPRT overexpression was not correlated to increased NAD + levels, suggesting NAD + independent mechanisms. We conclude that . QPRT, encoding a protein with anti-apoptotic properties, is a novel and direct target gene of WT1 in leukemic cells.

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author
organization
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Contribution to journal
publication status
published
subject
keywords
Acute myeloid leukemia, NAD+, Promoter, QPRT, Transcription, WT1
in
Biochemical and Biophysical Research Communications
volume
482
issue
4
pages
6 pages
publisher
Elsevier
external identifiers
  • scopus:85007449343
  • wos:000393720000043
ISSN
0006-291X
DOI
10.1016/j.bbrc.2016.11.114
language
English
LU publication?
yes
id
d2a7c9e4-26cc-448b-9ef5-52db9958af39
date added to LUP
2017-01-13 11:29:52
date last changed
2018-01-13 00:01:00
@article{d2a7c9e4-26cc-448b-9ef5-52db9958af39,
  abstract     = {<p>Wilms' tumor gene 1 (WT1) is a zinc finger transcription factor that has been implicated as an oncogene in leukemia and several other malignancies. When investigating possible gene expression network partners of . WT1 in a large acute myeloid leukemia (AML) patient cohort, one of the genes with the highest correlation to . WT1 was quinolinate phosphoribosyltransferase (QPRT), a key enzyme in the . de novo nicotinamide adenine dinucleotide (NAD+) synthesis pathway. To investigate the possible relationship between . WT1 and . QPRT, we overexpressed . WT1 in hematopoietic progenitor cells and cell lines, resulting in an increase of . QPRT expression. WT1 knock-down gave a corresponding decrease in . QPRT gene and protein expression. Chromatin-immunoprecipitation revealed WT1 binding to a conserved site in the first intron of the . QPRT gene. Upon overexpression in leukemic K562 cells, QPRT conferred partial resistance to the anti-leukemic drug imatinib, indicating possible anti-apoptotic functions, consistent with previous reports on glioma cells. Interestingly, the rescue effect of QPRT overexpression was not correlated to increased NAD + levels, suggesting NAD + independent mechanisms. We conclude that . QPRT, encoding a protein with anti-apoptotic properties, is a novel and direct target gene of WT1 in leukemic cells.</p>},
  author       = {Ullmark, Tove and Montano, Giorgia and Järvstråt, Linnea and Jernmark Nilsson, Helena and Håkansson, Erik and Drott, Kristina and Nilsson, Björn and Vidovic, Karina and Gullberg, Urban},
  issn         = {0006-291X},
  keyword      = {Acute myeloid leukemia,NAD+,Promoter,QPRT,Transcription,WT1},
  language     = {eng},
  month        = {01},
  number       = {4},
  pages        = {802--807},
  publisher    = {Elsevier},
  series       = {Biochemical and Biophysical Research Communications},
  title        = {Anti-apoptotic quinolinate phosphoribosyltransferase (QPRT) is a target gene of Wilms' tumor gene 1 (WT1) protein in leukemic cells},
  url          = {http://dx.doi.org/10.1016/j.bbrc.2016.11.114},
  volume       = {482},
  year         = {2017},
}