Human leukocyte elastase gene expression is regulated by PU.1 in conjunction with closely associated cytidine-rich and Myb binding sites

A Novel HLA-A*0201 Restricted Peptide Derived from Cathepsin G Is an Effective Immunotherapeutic Target in Acute Myeloid Leukemia

“…Furthermore, there was no correlation between CG expression and NE or P3 expression. Because CG is located on a different chromosome (chromosome 14) than NE and P3 (33, 34), which are both located on chromosome 19 (35, 36), and since CG is expressed later than NE and P3 during the maturation of the myeloid progenitor under the regulation of a different promoter than NE and P3 (20, 37), it is not surprising that levels of NE and P3 did not correlate with CG expression. Furthermore, we demonstrate higher expression of CG in primary AML than in normal granulocytes (Fig.…”

The proximal promoter of the human cathepsin G gene conferring myeloid-specific expression includes C/EBP, c-myb and PU.1 binding sites

“…Both proteinase 3 and leukocyte elastase promoters contain a similar GC-rich element, to which an unknown 40kDa protein is bound (Sturrock et al, 1996) (Sturrock et al, 2004). It is therefore likely that a common 40kDa protein binds to the GC-rich element in the proteinase 3, elastase and cathepsin G promoter.…”

“…PU.1 is a myeloid master regulator involved in the regulation of many myeloid specific genes, and PU.1 is together with C/EBPα essential for differentiation into the granulocytic lineage (Sturrock et al, 2004) (Borregaard et al, 2001). Paradoxically, C/EBPα can antagonize PU.1 in the lineage choice into neutrophilic differentiation, whereas PU.1 activity is more important for monocytic differentiation (Reddy et.…”

“…The modified constructs were transfected to U937 and NB4 cells, followed by measurements of the luciferase activity. Moreover, the GC-rich element at -86 bp was mutated, since a similar sequence is important for expression of proteinase 3 and leukocyte elastase genes (Sturrock et al, 1996) (Sturrock et al, 2004).…”

“…Rather, it has been proposed that differentiation-related transcriptional control of the expression of the cathepsin G gene and other granule components, results in sorting into distinct granule subtypes (Arnljots et al, 1998). Identification of important transactivating factors for the promyelocyte specific expression of elastase and proteinase 3 have been reported (Lutz et al, 2001;Nuchprayoon et al, 1997;Oelgeschlager et al, 1996;Sturrock et al, 1996;Sturrock et al, 2004). These factors include the trancriptional activators PU.1, cmyb, C/EBP and a 40 kDa protein binding to a GC-rich cis-element.…”