RRC ID 54351
Author Yamazaki S, Muta T, Takeshige K.
Title A novel IkappaB protein, IkappaB-zeta, induced by proinflammatory stimuli, negatively regulates nuclear factor-kappaB in the nuclei.
Journal J Biol Chem
Abstract The transcription factor nuclear factor-kappaB (NF-kappaB) plays crucial roles in a wide variety of cellular functions and its activity is strictly regulated by cytosolic inhibitors known as IkappaBs. We here report a new member of the IkappaB protein family, IkappaB-zeta, harboring six ankyrin repeats at its carboxyl terminus. IkappaB-zeta mRNA is strongly induced after stimulation by lipopolysaccharide. The induction of IkappaB-zeta is also observed by stimulation with interleukin-1beta but not by tumor necrosis factor-alpha. In contrast to cytosolic IkappaB-alpha, -beta, and -epsilon, the induced IkappaB-zeta localizes in the nucleus via its amino-terminal region, which shows no homology with other proteins. Transiently expressed IkappaB-zeta inhibits the NF-kappaB activity without affecting the nuclear translocation of NF-kappaB upon stimulation. The expressed IkappaB-zeta preferentially associates with the NF-kappaB subunit p50 rather than p65 and recombinant IkappaB-zeta proteins inhibit the DNA binding of the p65/p50 heterodimer and the p50/p50 homodimer. Thus, IkappaB-zeta negatively regulates NF-kappaB activity in the nucleus, possibly in order to prevent excessive inflammation. Moreover, transfection of IkappaB-zeta renders cells more susceptible to apoptosis induced by tumor necrosis factor-alpha. The proapoptotic activity of IkappaB-zeta further suggests that it might be one of key regulators for inflammation and other biologically relevant processes.
Volume 276(29)
Pages 27657-62
Published 2001-7-20
DOI 10.1074/jbc.M103426200
PII S0021-9258(20)89900-1
PMID 11356851
MeSH Amino Acid Sequence Animals Base Sequence Cell Nucleus / metabolism* DNA Primers I-kappa B Proteins / biosynthesis I-kappa B Proteins / physiology* Lipopolysaccharides / pharmacology* Macrophages, Peritoneal / drug effects Macrophages, Peritoneal / metabolism Mice Molecular Sequence Data NF-kappa B / metabolism* Protein Isoforms / biosynthesis Protein Isoforms / physiology* RNA, Messenger / genetics Sequence Homology, Amino Acid
IF 4.238
Times Cited 198
DNA material pcDNA3-FLAG-mouse p50 (RDB16743) pcDNA3-FLAG-mouse p65 (RDB16729)