| 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
|
| Resource |
| DNA material |
pcDNA3-FLAG-mouse p50 (RDB16743)
pcDNA3-FLAG-mouse p65 (RDB16729) |
