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

Tove Ullmark, Giorgia Montano, Linnea Järvstråt, Helena Jernmark Nilsson, Erik Håkansson, Kristina Drott, Björn Nilsson, Karina Vidovic, Urban Gullberg

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review

13 Citeringar (SciVal)
212 Nedladdningar (Pure)

Sammanfattning

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.

Originalspråkengelska
Sidor (från-till)802–807
Antal sidor6
TidskriftBiochemical and Biophysical Research Communications
Volym482
Utgåva4
Tidigt onlinedatum2016 nov. 11
DOI
StatusPublished - 2017 jan. 22

Ämnesklassifikation (UKÄ)

  • Hematologi

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