Interaction between hnRNPA1 and IkappaBalpha is required for maximal activation of NF-kappaB-dependent transcription

Molecular and Cellular Biology
D C HayR T Hay

Abstract

Transcriptional activation of NF-kappaB is mediated by signal-induced phosphorylation and degradation of its inhibitor, IkappaBalpha. NF-kappaB activation induces a rapid resynthesis of IkappaBalpha which is responsible for postinduction repression of transcription. Following resynthesis, IkappaBalpha translocates to the nucleus, removes template bound NF-kappaB, and exports NF-kappaB to the cytoplasm in a transcriptionally inactive form. Here we demonstrate that IkappaBalpha 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 IkappaBalpha. Cells lacking hnRNPA1 are defective in NF-kappaB-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 IkappaBalpha 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-kappaB-dependent transcription.

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Citations

Apr 3, 2009·Genes & Development·Xicheng MaoEzra Burstein
Apr 15, 2004·Molecular and Cellular Biology·Maria T Vassileva, Michael J Matunis
Sep 26, 2013·International Journal of Molecular Sciences·Jacques Jean-PhilippeMassimo Caputi
Nov 19, 2008·Neurochemical Research·Zheng-Yu PengPing Xu
May 8, 2007·Fertility and Sterility·Zhen HouJiayin Liu
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Jan 16, 2007·Molecular Carcinogenesis·Paromita RoychoudhuryKeya Chaudhuri
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Aug 6, 2004·The Journal of Biological Chemistry·Véronique BériaultAndrew J Mouland
Oct 2, 2020·Molecular Neurobiology·Yi-Hua LowTammaryn Lashley
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Jul 24, 2012·International Journal of Cancer. Journal International Du Cancer·Zheng-Jun ZhouJia Fan
Jan 14, 2021·International Journal of Molecular Sciences·Emma I Kane, Donald E Spratt
Dec 28, 2005·Biochimica Et Biophysica Acta·Brian CarpenterGraeme I Murray

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