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STAT1 exists in phosphorylated (pSTAT1) and unphosphorylated (uSTAT1) forms each regulated by IFN-γ. Although STAT1 is a key mediator of the IFN-γ signaling pathway, an essential component of the host cancer immunosurveillance system, STAT1 is also overexpressed in certain human cancers where the functions of pSTAT1 and uSTAT1 are ill defined. Using a(More)
IFN regulatory factor 8 (IRF8) is a key transcription factor for myeloid cell differentiation and its expression is frequently lost in hematopoietic cells of human myeloid leukemia patients. IRF8-deficient mice exhibit uncontrolled clonal expansion of undifferentiated myeloid cells that can progress to a fatal blast crisis, thereby resembling human chronic(More)
Tumor escape and recurrence are major impediments for successful immunotherapy. It is well-documented that the emergence of Ag-loss variants, as well as regulatory mechanisms suppressing T cell function, have been linked to inadequate antitumor activity. However, little is known regarding the role of Fas-mediated cytotoxicity by tumor-specific CD8(+) CTL in(More)
Fas is a member of the death receptor family. Stimulation of Fas leads to induction of apoptotic signals, such as caspase 8 activation, as well as "non-apoptotic" cellular responses, notably NF-κB activation. Convincing experimental data have identified NF-κB as a critical promoter of cancer development, creating a solid rationale for the development of(More)
1Department of Biochemistry and Molecular Biology, 2Department of Biostatistics and Epidemiology and 3Department of Pathology, Medical College of Georgia, Georgia Health Sciences University, Augusta, GA 30912, USA, 4Charles Norwood VA Medical Center, Augusta, GA 30904, USA, 5Sarcoma Research Center and 6Department of Cancer Biology, The University of Texas(More)
IFN regulatory factor 8 (IRF8) is both constitutively expressed and IFN-gamma inducible in hematopoietic and nonhematopoietic cells. We have shown that IRF8 expression is silenced by DNA methylation in human colon carcinoma cells, but the molecular mechanism underlying methylation-dependent IRF8 silencing remains elusive. In this study, we observed that(More)
IFN regulatory factor 8 (IRF8) is a transcription factor that was originally identified in myeloid cells and has been shown to be essential for differentiation and function of hemopoietic cells. Mice with a null mutation of IRF8 exhibit uncontrolled expansion of the granulocytic and monocytic lineages that progress into a phenotype resembling human chronic(More)
A prominent phenotype of IRF8 knockout (KO) mice is the uncontrolled expansion of immature myeloid cells. The molecular mechanism underlying this myeloproliferative syndrome is still elusive. In this study, we observed that Bax expression level is low in bone marrow preginitor cells and increases dramatically in primary myeloid cells in wt mice. In(More)