| Autor: |
Arlt, Alexander, Kruse, Marie-Luise, Breitenbroich, Maike, Gehrz, Andre, Koc, Bulent, Minkenberg, Jorg, Folsch, Ulrich R, Schafer, Heiner |
| Předmět: |
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| Zdroj: |
Oncogene; 5/22/2003, Vol. 22 Issue 21, p3343, 9p |
| Abstrakt: |
The early response gene IEX-1 is involved in the regulation of cellular growth and survival, and its expression is related to stress-, growth- and death-inducing signals. Addressing the role of IEX-1 in the promotion of apoptosis, we investigated the effect of IEX-1 on nuclear factor-?B (NF-?B) activation. Stably transfected HEK-293 cells conditionally overexpressing IEX-1 exhibit decreased levels of NF-?B activity, either basal or TNFa induced, as shown by gel-shift and luciferase reporter gene assay. Furthermore, activated p65 accumulated in the nuclei of 293 cells to a lower degree, if IEX-1 expression was increased. This inhibited NF-?B activation was preceded by an altered turnover of I?Ba and phospho-I?Ba. In addition, IEX-1 expression also inhibited the activity of the 26S-proteasome, as shown by a fluorometric proteasome assay. Conversely, disruption of IEX-1 expression in 293 cells by stable transfection with specific anti-IEX-1 hammerhead ribozymes increased NF-?B activity, and accelerated the degradation of I?Ba. Along with these opposite effects of IEX-1 expression and IEX-1 disruption on NF-?B activation, the sensitivity of 293 cells towards various apoptotic stimuli also changed. In contrast to ribozyme-transduced 293 cells that were significantly less sensitive to apoptosis, this sensitivity was enhanced if IEX-1 expression was increased. Our data suggest that IEX-1 - itself an NF-?B target gene - inhibits the activation of this transcription factor, and hereby may counteract the antiapoptotic potential of NF-?B.Oncogene (2003) 22, 3343-3351. doi:10.1038/sj.onc.1206524 [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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