Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.22.1 (DNase II)
 429 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several recent studies have suggested that intracellular deoxyribonuclease II (DNase II) is responsible for the degradation of DNA from apoptotic cells that are engulfed by macrophages. In this study, we studied DNase II expression during the phorbol 12-myristate-13-acetate (PMA)-induced differentiation of HL-60 and THP-1 cells. Basal levels of DNase II mRNA and protein were low, with expression being up-regulated approximately 15- and 7-fold, respectively, in HL-60 and THP-1 cells 72 h after PMA treatment. Nuclear run-on and luciferase reporter assays showed that transcription of DNase II gene was increased in PMA-treated cells. Together, these results demonstrate that DNase II gene transcription is increased during myelomonocytic differentiation, resulting in increased levels of mRNA and protein. This increase in DNase II levels in differentiated HL-60 and THP-1 cells suggests that it may play an important role in macrophages.
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PMID:Up-regulation of human deoxyribonuclease II gene expression during myelomonocytic differentiation of HL-60 and THP-1 cells. 1214 25

Expression of DNase II in macrophages is potentially crucially important in the removal of unwanted DNA. We have previously shown that DNase II expression is up-regulated at the transcriptional level during the phorbol 12-myristate-13-acetate (PMA)-induced differentiation of HL-60 and THP-1 cells. In this study, we investigated the cis-regulatory elements and transcription factors involved in this process in HL-60 cells. cis-Regulatory elements in the DNase II promoter were located by 5' deletion and site-directed mutagenesis of promoter-luciferase constructs and transient transfection of HL-60 cells. Furthermore, the binding proteins were identified by electrophoretic mobility shift assay (EMSA) in the presence of specific antibodies. In the DNase II promoter, 249 base pairs upstream of the transcription start site were essential for maximal promoter activity in both untreated and PMA-treated HL-60 cells and, within this region, three Sp1 and Sp3 binding sites were identified as essential for transcriptional regulation and PMA induction. Western blot analysis showed that PMA treatment resulted in increased levels of Sp1 and Sp3 proteins. Furthermore, cotransfection analysis in Drosophila SL2 cells showed that Sp1 was more potent than Sp3 in activating the DNase II promoter. We therefore conclude that Sp1 and/or Sp3 are involved in the up-regulation of DNase II expression during the differentiation of HL-60 cells.
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PMID:Sp1 and Sp3 are involved in up-regulation of human deoxyribonuclease II transcription during differentiation of HL-60 cells. 1269 99