Nucling interacts with nuclear factor-kappaB, regulating its cellular distribution.
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.
Liu
Li
L
Division of Enzyme Pathophysiology, Institute for Enzyme Research, University of Tokushima, Japan.
Sakai
Takashi
T
Tran
Nam Hoang
NH
Mukai-Sakai
Rika
R
Kaji
Ryuji
R
Fukui
Kiyoshi
K
D000818:Animals; D019556:COS Cells; D002467:Cell Nucleus; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D003593:Cytoplasm; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018613:Microscopy, Confocal; D016328:NF-kappa B / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014162:Transfection
D008565:Membrane Proteins; D016328:NF-kappa B; D012333:RNA, Messenger; C483107:Uaca protein, mouse