| First Author | Liu L | Year | 2009 |
| Journal | FEBS J | Volume | 276 |
| Issue | 5 | Pages | 1459-70 |
| PubMed ID | 19187222 | Mgi Jnum | J:147886 |
| Mgi Id | MGI:3842869 | Doi | 10.1111/j.1742-4658.2009.06888.x |
| Citation | Liu L, et al. (2009) Nucling interacts with nuclear factor-kappaB, regulating its cellular distribution. FEBS J 276(5):1459-70 |
| abstractText | Nucling is an Apaf1-binding proapoptotic protein involved in apoptosome-mediated apoptosis. Luciferase assays have revealed that the activation of nuclear factor-kappaB induced by tumor necrosis factor-alpha, interleukin-1beta and lipopolysaccharide is downregulated by the overexpression of Nucling in HEK293 cells. Moreover, the expression of endogenous cyclooxygenase 2, tumor necrosis factor-alpha and galectin-3, the end-point molecules in the pathway for the activation of nuclear factor-kappaB, as well as nuclear factor-kappaB (p65) itself, is upregulated in Nucling gene-deficient mouse embryonic fibroblasts, suggesting that nuclear factor-kappaB is a target of Nucling. Subsequent study has revealed that Nucling physically interacts with nuclear factor-kappaB (p65 and p50) and that the binding domain of Nucling is its amino-terminal region (amino acids 1-466) containing ankyrin repeats. Overexpression of Nucling prevents the translocation of nuclear factor-kappaB into the nucleus. In addition, the cytoplasmic retention of endogenous nuclear factor-kappaB in resting cells is not observed in Nucling gene-deficient mouse embryonic fibroblasts. These results reveal a novel function of Nucling as a suppressor of nuclear factor-kappaB, mediated by its cytoplasmic retention through physical interaction. |
