Conserved gene structure and transcription factor sites in the human and mouse deoxycytidine kinase genes¹

Abstract

Deoxycytidine kinase (dCK) phosphorylates several anti-cancer and anti-viral nucleoside analogs. The enzyme is predominantly expressed in lymphoid tissues regulated by an unknown mechanism. We have cloned and sequenced the 20 kbp mouse dCK gene and W W1.7 kbp of the 5P P flanking regions of both the human and mouse dCK genes. Five major inter-species conserved motifs were identified in the 5P P region including the transcription initiation region, an SP1 site and two closely located putative octamer transcription factor sites. Luciferase reporter experiments showed that the human dCK 5P P region efficiently initiated transcription but no tissue regulatory element could be identified. ß

Functional role of alternatively spliced deoxycytidine kinase in sensitivity to cytarabine of acute myeloid leukemic cells

“…The gene encoding human dCK consists of 7 exons 4 under the control of ubiquitously expressed transcription factors such as Sp1 and E2F. [5][6][7] dCK is expressed in the cytoplasm of most mammalian cells, with highest expression in thymus and T-lymphocyte lineages. 8,9 Patients with AML are treated with combination chemotherapy consisting of AraC and an anthracycline antibiotic (eg, daunorubicin, idarubicin), occasionally supplemented by a third drug.…”

The clinical implication of single nucleotide polymorphisms in deoxycytidine kinase in chronic hepatitis B patients treated with lamivudine

“…The dCK gene resides on the short arm of chromosome 4(4q13.3–q21.1). It has seven exons and extends over 34 kb [Chen et al, ; Johansson et al, ; Baker et al, ]. Interestingly, SNPs of dCK gene were reported as genetic markers for prediction of chemotherapy responsiveness in acute myeloid leukemia patients [Veuger et al, ; Shi et al, ].…”