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Molecular and Cellular Biology, May 2001, p. 3482-3490, Vol. 21, No. 10
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.10.3482-3490.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Interaction between hnRNPA1 and Ikappa Balpha Is Required for Maximal Activation of NF-kappa B-Dependent Transcription

David C. Hay,1 Graham D. Kemp,1 Catherine Dargemont,2 and Ronald T. Hay1,*

Institute of Biomolecular Sciences, School of Biology, University of St. Andrews, The North Haugh, St. Andrews, KY16 9ST, Scotland,1 and Institut Jacques Monod, UMR 7592, 75251 Paris Cedex 05, France2

Received 30 October 2000/Returned for modification 13 November 2000/Accepted 20 February 2001

Transcriptional activation of NF-kappa B is mediated by signal-induced phosphorylation and degradation of its inhibitor, Ikappa Balpha . NF-kappa B activation induces a rapid resynthesis of Ikappa Balpha which is responsible for postinduction repression of transcription. Following resynthesis, Ikappa Balpha translocates to the nucleus, removes template bound NF-kappa B, and exports NF-kappa B to the cytoplasm in a transcriptionally inactive form. Here we demonstrate that Ikappa Balpha interacts directly with another nucleocytoplasmic shuttling protein, hnRNPA1, both in vivo and in vitro. This interaction requires one of the N-terminal RNA binding domains of hnRNPA1 and the C-terminal region of Ikappa Balpha . Cells lacking hnRNPA1 are defective in NF-kappa B-dependent transcriptional activation, but the defect in these cells is complemented by ectopic expression of hnRNPA1. hnRNPA1 expression in these cells increased the amount of Ikappa Balpha degradation, compared to that of the control cells, in response to activation by Epstein-Barr virus latent membrane protein 1. Thus in addition to regulating mRNA processing and transport, hnRNPA1 also contributes to the control of NF-kappa B-dependent transcription.


* Corresponding author. Mailing address: Institute of Biomolecular Sciences, School of Biology, University of St. Andrews, The North Haugh, St. Andrews, KY16 9ST, Scotland, United Kingdom. Phone: 44 1334 463396. Fax: 44 1334 462595. E-mail: rth{at}st-and.ac.uk.


Molecular and Cellular Biology, May 2001, p. 3482-3490, Vol. 21, No. 10
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.10.3482-3490.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.



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