Dual roles of orphan nuclear receptor TR3/Nur77/NGFI-B in mediating cell survival and apoptosis.

As a transcriptional factor, Nur77 has sparked interests across different research fields in recent years. A number of studies have demonstrated the functional complexity of Nur77 in mediating survival/apoptosis in a variety of cells, including tumor cells. Conflicting observations also exist in clinical reports, in that TR3 behaves like an oncogene in tumors of the GI tract, lung, and breast, that is negatively associated with tumor stage and patient prognosis; while functions as a tumor suppressor gene in malignancies of the hematological and lymphatic system, skin, and ovary whose malfunction results in carcinogenesis. This chapter summarizes the apparent opposing effects of Nur77 on cells and explicates the mechanisms that determine the functional preference of Nur77. We conclude that in addition to cell type and agent context, other factors such as cellular localization, signaling pathway, and posttranslational modification also determine the final effects of Nur77 on cells.