Negative cross-talk between the human orphan nuclear receptor Nur77/NAK-1/TR3 and nuclear factor-kappaB.
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Harant, Hanna and Lindley, Ivan-J.D. (2004) Negative cross-talk between the human orphan nuclear receptor Nur77/NAK-1/TR3 and nuclear factor-kappaB. Nucleic Acids Research, 32 (17). pp. 5280-5290. ISSN 1362-4962
Abstract
The effect of orphan nuclear receptor Nur77 overexpression on activation of an interleukin-2 (IL-2) promoter-luciferase construct was analyzed in the human leukemic cell line Jurkat. Cotransfection of the IL-2 promoter construct together with the Nur77 expression plasmid resulted in a significant repression of IL-2 promoter activation compared to control cells. The repression by Nur77 requires the N-terminal activation function-1 domain. The repressive effect of Nur77 on IL-2 promoter activation is mediated through inhibition of the transcription factor complex nuclear factor-kappaB (NF-kappaB), since blocking or alteration of the IL-2 NF-kappaB binding sites resulted in abrogation of the repressive effect of Nur77. Moreover, further examination of a reporter gene construct containing multiple copies of the IL-2 CD28 response element (CD28RE) showed that Nur77 can inhibit transactivation mediated by the NF-kappaB components p65 and c-Rel. However, no effect of Nur77 was seen on p65-mediated transactivation of a construct containing multiple NF-kappaB binding sites of the HIV LTR. Our data suggest that Nur77 is able to block activation through NF-kappaB when bound to low-affinity NF-kappaB binding sites, such as those located in the IL-2 promoter.
| Item Type: | Article |
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| Additional Information: | free full text available at publisher's official URL and at PubMedCentral; doi:10.1093/nar/gkh856 Publisher version can be used for Nucleic Acids Research articles |
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| Date Deposited: | 13 Oct 2015 13:17 |
| Last Modified: | 13 Oct 2015 13:17 |
| URI: | https://oak.novartis.com/id/eprint/41 |