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C/EBPalpha S248A mutation reduces granulocytic differentiation in human leukemic K562 cells |
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| Authors: | Singh Sheo M Trivedi A K Behre Gerhard |
| Affiliation: | a Bone Marrow Transplantation Section, State Center for Cell and Gene Therapy, Department of Internal Medicine IV, Martin-Luther-University, Ernst Grube Str. 40, Halle 06097, Germany b Department of Gene and Cell Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA c DTDD Division, Central Drug Research institute (CDRI), Lucknow 226001, India |
| Abstract: | Phosphorylation of C/EBPα can either lead to granulocytic differentiation or a block in granulopoiesis. This dichotomy in effect is dependent on the upstream signaling pathway and the phosphorylation site in C/EBPα. Ras signaling induced phosphorylation of S248 residue of C/EBPα is known to enhance granulocytic differentiation. In this study, using β-estradiol inducible stable cell lines we show that the point mutation of phosphorylation site S248 in C/EBP disrupts the CD11b and GCSFr expression and subsequently reduces the differentiation of leukemic K562 cells. Based on our observations in the present study, we conclude that S248A mutation of C/EBPα leads to a reduction of granulocytic differentiation markers and a block in differentiation at the morphological level. |
| Keywords: | C/EBPα Acute myeloid leukemia Granulocytes |
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