Charlotte Lindenblatt

Heinrich-Heine-Universität Düsseldorf, Düsseldorf, North Rhine-Westphalia, Germany

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Publications (2)9.89 Total impact

  • Charlotte Lindenblatt, Klaus Schulze-Osthoff, Gudrun Totzke
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    ABSTRACT: IkappaBzeta belongs to the nuclear members of the IkappaB protein family. Its function in regulating the activity of the transcription factor NFkappaB is poorly understood. Here, we demonstrate that human IkappaBzeta is posttranscriptionally regulated by microRNA (miR)-124a. In HepG2 cells miR-124a was not endogenously expressed, but upon enforced expression dramatically inhibited the interleukin-1beta-induced protein expression of IkappaBzeta. The predicted binding site for miR-124a in the 3'UTR of the IkappaBzeta mRNA revealed an imperfect match resulting in miR-124a-mediated suppression of IkappaBzeta expression through translational repression. Reporter gene analyses revealed that miR-124a targets IkappaBzeta mRNA through base pairing to the partially complementary sequence in the 3'UTR that was predicted as a binding site by in silico analysis. Furthermore, we demonstrate that the 7mer seed match is sufficient for recognition of the IkappaBzeta mRNA. Together, our data identify IkappaBzeta as a target of miR-124a that might be involved in the fine-tuning of NF-kappaB-mediated gene expression.
    Cell cycle (Georgetown, Tex.) 08/2009; 8(13):2019-23. · 5.24 Impact Factor
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    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 cells more resistant to apoptosis, whereas overexpression of IkappaB-zeta was sufficient to induce cell death. Our results, therefore, suggest that IkappaB-zeta functions as an additional regulator of NF-kappaB activity and, hence, provides another control level for the activation of NF-kappaB-dependent target genes.
    Journal of Biological Chemistry 06/2006; 281(18):12645-54. · 4.65 Impact Factor