The involvement of FOXO and STAT in DNA PKcs and

The involvement of FOXO3 and STAT5 in DNA-PKcs and SP 141 IV has not been reported before, and the search by the ECR browser (http://ecrbrowser.decode.org) revealed that 1kb of the 5′ promoter of DNA-PKcs possesses 4 STAT (−908bp to −901bp, −676bp to −656bp, −533bp to −526bp and −66bp to −59bp) and no FOXO binding site, whereas the 5′ promoter of DNA ligase IV we analyzed possesses no STAT or FOXO binding sites. The effect of STAT binding site (−66bp to −59bp) was negligible (Fig. 3b), however, our preliminary analysis revealed that other two sites (−676bp to −656bp, and −533bp to −526bp) were responsible for some promoter activity (data not shown). However, the important point is that the difference in the DNA-PKcs promoter activity between K562 and K562/DNR was derived from the region between −49bp and the first exon. The reason for the absence of MDR overexpression in HL60/DNR cells is not known but the absence of an important transcription factor would be suspected. Inhibitors against DNA-PKcs, ATM and MDR1 protein have been reported to overcome fludarabine resistance in CLL cells [57]. Thus, it seems likely that components of NHEJ including DNA-PKcs and DNA ligase IV or their common transcription factor, Sp1, are the medicinally treatable target for overcoming the MDR phenotype. However, further work is needed to rule out unexpected adverse effects by inhibiting housekeeping transcription factors such as Sp1.
Conclusion The following are the supplementary data related to this article.