A novel member of the IkappaB family, human IkappaB-zeta, inhibits transactivation of p65 and its DNA binding

The Journal of Biological Chemistry
Gudrun TotzkeKlaus Schulze-Osthoff

Abstract

A novel member of the IkappaB family, human IkappaB-zeta, was identified by a differential screening approach of apoptosis-sensitive and -resistant tumor cells. The protein consists of 6 ankyrin repeats at its COOH terminus and shares about 30% identity with other IkappaB members. IkappaB-zeta associates with both the p65 and p50 subunit of NF-kappaB and inhibits the transcriptional activity as well as the DNA binding of the transcription factor. Interestingly, IkappaB-zeta is localized in the nucleus where it aggregates in matrix-associated deacetylase bodies, indicating that IkappaB-zeta regulates nuclear NF-kappaB activity rather than its nuclear translocation from the cytoplasm. IkappaB-zeta expression itself was regulated by NF-kappaB, suggesting that its activity is controlled in a negative feedback loop. Unlike classical IkappaB proteins, IkappaB-zeta was not degraded upon cell stimulation. Treatment with tumor necrosis factor-alpha, interleukin-1beta, and lipopolysaccharide induced a strong induction of IkappaB-zeta transcripts. Expression of IkappaB-zeta was detected in different tissues including lung, liver, and in leukocytes but not in the brain. Suppression of endogenous IkappaB-zeta by RNA interference rendered ce...Continue Reading

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