UXT is a novel and essential cofactor in the NF-κB transcriptional enhanceosome

Sun, Shaogang; Tang, Yujie; Lou, Xiwen; Zhu, Lianhui; Yang, Kun; Zhang, Bianhong; Shi, Hao; Wang, Chen

doi:10.1083/jcb.200611081

Cited by 56 publications

(84 citation statements)

References 52 publications

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“…There might be a link between these observations and a recent paper that states that UXT is part of the NF-κB enhanceosome (Sun et al 2007). Though the authors favored a model where UXT interacts directly with the p65 subunit of NF-κB, many of the results (NF-κB-dependent transcription, subcellular NF-κB localization, TNFα-mediated apoptosis) might be explained by a RPAP3/R2TP/prefoldin-like complex-dependent regulation of the activity of upstream MEKK3 activator.…”

Section: Map3k3 (Mekk3)mentioning

confidence: 74%

New insights into the biogenesis of nuclear RNA polymerases?This paper is one of a selection of papers published in this special issue entitled “Canadian Society of Biochemistry, Molecular & Cellular Biology 52nd Annual Meeting — Protein Folding: Principles and Diseases” and has undergone the Journal's usual peer review process.

Cloutier

Coulombe

2010

Biochem. Cell Biol.

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More than 30 years of research on nuclear RNA polymerases (RNAP I, II, and III) has uncovered numerous factors that regulate the activity of these enzymes during the transcription reaction. However, very little is known about the machinery that regulates the fate of RNAPs before or after transcription. In particular, the mechanisms of biogenesis of the 3 nuclear RNAPs, which comprise both common and specific subunits, remains mostly uncharacterized and the proteins involved are yet to be discovered. Using protein affinity purification coupled to mass spectrometry (AP-MS), we recently unraveled a high-density interaction network formed by nuclear RNAP subunits from the soluble fraction of human cell extracts. Validation of the dataset using a machine learning approach trained to minimize the rate of false positives and false negatives yielded a highconfidence dataset and uncovered novel interactors that regulate the RNAP II transcription machinery, including a set of proteins we named the RNAP II-associated proteins (RPAPs). One of the RPAPs, RPAP3, is part of an 11-subunit complex we termed the RPAP3/R2TP/prefoldin-like complex. Here, we review the literature on the subunits of this complex, which points to a role in nuclear RNAP biogenesis.

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Section: Map3k3 (Mekk3)mentioning

confidence: 74%

New insights into the biogenesis of nuclear RNA polymerases?This paper is one of a selection of papers published in this special issue entitled “Canadian Society of Biochemistry, Molecular & Cellular Biology 52nd Annual Meeting — Protein Folding: Principles and Diseases” and has undergone the Journal's usual peer review process.

Cloutier

Coulombe

2010

Biochem. Cell Biol.

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“…4B). Besides, UXT was recently uncovered as an integral component of NF-kB enhanceosome (21). Neither could CITED2 promote the export of NF-kB from the nucleus to the cytoplasm or actively retain NF-kB in the nucleus, whereas IkBa (SR) (Fig.…”

Section: Cited2 Prevents P65 From Binding To Its Cognate Promotersmentioning

confidence: 99%

“…p300 was a gift from Dr. Warner C. Greene (University of California, San Francisco, CA). p65 tagged with or without FLAG, FLAGIkBaSR, FLAG-TRAF6, FLAG-MyD88, and the reporter gene 3*kB-luc have been described previously (21). The CITED2 (human) siRNA sequences were as follows: CITED2 (396), 59-CCACUACAUGCCGGA-UUUG-39; mCITED2 (396m), 59-CCACUACACACCGGAUUUG-39.…”

Section: Plasmids and Sirnasmentioning

confidence: 99%

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Negative Feedback Regulation of NF-κB Action by CITED2 in the Nucleus

Lou

Sun

Chen

et al. 2011

The Journal of Immunology

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NF-κB is a family of important transcription factors that modulate immunity, development, inflammation, and cancer. The biological activity of NF-κB is subjected to various spatial and temporal regulations. Bioinformatics analysis predicts that CITED2 is topologically close to NF-κB in the protein interaction networks. In this study, we show that ectopic expression or knockdown of CITED2 attenuates or potentiates, respectively, the expression of NF-κB–responsive genes. Mechanistically, CITED2 constitutively localizes inside the nucleus and interacts specifically with the coactivator p300. This prevents p65 from binding to p300, impairs p65 acetylation, and attenuates p65 binding to its cognate promoters. Furthermore, LPS induces CITED2 expression via NF-κB in macrophages. CITED2 sensitizes cells to TNF-α–induced apoptosis. Collectively, this study identifies CITED2 as a novel regulator of NF-κB in the nucleus, which reveals a negative feedback mechanism for NF-κB signaling.

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“…The following promoter-specific primers were used: human IP-10, sense (ACA GTT CAT GTT TTG GAA AGT) and antisense (TCC CTA ATT CTG ATT GGA TAA). primers used to amplify the human A20 and GAPDH promoters were synthesized as described previously [41].…”

Section: Chip Assaymentioning

confidence: 99%

Dishevelled interacts with p65 and acts as a repressor of NF-κB-mediated transcription

Deng

Wang

et al. 2010

Cell Res

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Dishevelled (Dvl) is a highly conserved protein family that plays an important role in mediating Wnt signaling from membrane to cytoplasm. Recently we reported that Dvl also functions in the nucleus by stabilizing the β-catenin/TCFs transcriptional complex. Here we describe that Dvl may function as a repressor of NF-κB. Our data show that Dvl directly binds to p65 and their interaction occurs in the nucleus. Dvl expression inhibits p65-mediated or TNF-α-stimulated activation of the NF-κB dependent reporter. This action of Dvl, however, is not dependent on Wnt or its downstream effector β-catenin. Chromatin immunoprecipitation assay shows that recruitment of p65 to the promoters of NF-κB target genes is significantly enhanced when expression of Dvl is knocked down. Consistently, the expression level of a subset of NF-κB target genes is also increased after knock-down of Dvl. Moreover, our data suggest that Dvl may relieve the anti-apoptotic effect of NF-κB, thus play a role in promoting apoptosis. Therefore, this work demonstrates a novel function of Dvl in modulating NF-κB-regulated gene transcription.

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UXT is a novel and essential cofactor in the NF-κB transcriptional enhanceosome

Cited by 56 publications

References 52 publications

Negative Feedback Regulation of NF-κB Action by CITED2 in the Nucleus

Dishevelled interacts with p65 and acts as a repressor of NF-κB-mediated transcription

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