Regulation of jun Expression and Activation of AP-1 Activity by Erythropoietin

Erythropoietin (EPO) is a molecule which regulates hemoglobin gene expression during erythroid proliferation and differentiation. However, the mechanism by which it regulates gene expression is poorly understood. Secondly, unlike other hematopoietic factors which induce expression of early response genes, it is unknown whether EPO is capable of inducing the expression and activation of early response genes. In this study, evidence is presented that EPO induces the expression of early response genes c-jun, junD and c-fos mRNA, stimulates jun protein synthesis and induces activation of 5 × AP-1/CAT activity in human erythroleukemia K562 cells. Also, EPO appears to regulate jun expression at transcriptional, post transcriptional and translational levels. These observations suggest that jun and fos expression may be relevant in the mechanism of growth control by EPO.