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Nucling interacts with nuclear factor‐κB, regulating its cellular distribution
Author(s) -
Liu Li,
Sakai Takashi,
Tran Nam Hoang,
MukaiSakai Rika,
Kaji Ryuji,
Fukui Kiyoshi
Publication year - 2009
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2009.06888.x
Subject(s) - transcription factor , biology , microbiology and biotechnology , nuclear protein , ankyrin repeat , endogeny , nuclear export signal , tumor necrosis factor alpha , cell nucleus , cytoplasm , chemistry , gene , biochemistry , immunology
Nucling is an Apaf1‐binding proapoptotic protein involved in apoptosome‐mediated apoptosis. Luciferase assays have revealed that the activation of nuclear factor‐κB induced by tumor necrosis factor‐α, interleukin‐1β and lipopolysaccharide is downregulated by the overexpression of Nucling in HEK293 cells. Moreover, the expression of endogenous cyclooxygenase 2, tumor necrosis factor‐α and galectin‐3, the end‐point molecules in the pathway for the activation of nuclear factor‐κB, as well as nuclear factor‐κB (p65) itself, is upregulated in Nucling gene‐deficient mouse embryonic fibroblasts, suggesting that nuclear factor‐κB is a target of Nucling. Subsequent study has revealed that Nucling physically interacts with nuclear factor‐κB (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‐κB into the nucleus. In addition, the cytoplasmic retention of endogenous nuclear factor‐κB 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‐κB, mediated by its cytoplasmic retention through physical interaction.