| EDAG is a novel human hematopoietic tissue-specific gene. Previous studies showed that EDAG involves in the regulation of hematopoietic proliferation, differentiation and leukemogenesis. At present, studies focus on the function and molecular mechanism of EDAG. First, overexpression of EDAG in IL-3-dependent pro-B Ba/F3 cells prolonged survival and decreased the apoptosis consistent with the high expression of c-Myc, Bcl-2 and Bcl-xL in absence of IL-3. Using EMSA and luciferase reporter assay, we showed that the anti-apoptotic activity of EDAG was associated with enhanced NF-kB activity. PI3K pathway involves in the activation of NF-κB induced by EDAG. To further provide direct evidence for a role of EDAG in regulation of hematopoietic development, we selectively expressed EDAG cDNA in hematopoietic systems under the control of human CD11a promoter using a transgenic mouse model. The results indicated that overexpression of EDAG in mice affects the development of hematopoietic system characterized by enhanced myelopoiesis with myeloproliferative disease (MPD), inhibted lymphopoiesis, increased numbers of hematopoietic stem cells with reduced differentiation activity and DC cells. Also EDAG altered the expression of several hematopoiesis-related genes in transgenic mice. These results suggest that EDAG is a key regulator in the hematopoiesis. Furthermore, we also demonstrated that EDAD has transactivation activity in yeast and mammalian cells. PKC activator PMA treatment or cotransfection with EDAG-interacting protein THAP11 can enhance the transactivation activtity. Based on the DNA-binding activity of THAP11, we suppose that EDAG/THAP11 may serves as a novel transcription factor and phosphorylation modification is critical for its transactivation activity.Taken together, all the results suggest that EDAG is a novel transcription regulator and involves in the regulation of apoptosis and hematopoietic develpment...
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