Ribosomal Protein S3: A KH Domain Subunit in NF-κB Complexes that Mediates Selective Gene Regulation

Wan, Fengyi; Anderson, Darrell E.; Barnitz, R. Anthony; Snow, Andrew L.; Bidère, Nicolas; Zheng, Lixin; Hegde, Vijay; Lam, Lloyd T.; Staudt, Louis M.; Levens, David; Deutsch, Walter

doi:10.1016/j.cell.2007.10.009

Cited by 311 publications

(471 citation statements)

References 35 publications

Supporting

Mentioning

439

Contrasting

Unclassified

Order By: Relevance

“…Suppression of IL-8 by CHFR through the inhibition of NF-jB L Kashima et al these two complexes slightly (Figure 3a, lanes 5 and 6), indicating that complex I is a p65 homodimer and complex II is mainly composed of p65/p50 and p65/-c-Rel heterodimers, which is consistent with earlier reports (Sathe et al, 2004;Wan et al, 2007). Therefore, CHFR mainly affected the DNA-binding activity of the p65 homodimer ( Figure 3a, lane 2, complex I).…”

Section: Chfr Downregulates Nf-kb-dependent Transcriptionsupporting

confidence: 92%

CHFR, a potential tumor suppressor, downregulates interleukin-8 through the inhibition of NF-κB

et al. 2009

View full text Add to dashboard Cite

The mitotic checkpoint gene CHFR (checkpoint with forkhead and ring finger domains) is silenced in various human cancers by promoter hypermethylation, suggesting that CHFR is a tumor suppressor. Here, we show that CHFR functions as a negative regulator of the nuclear factor-jB (NF-jB) pathway. Expression of CHFR inhibited NF-jB reporter activity, whereas knockdown of CHFR activated reporter activity. These activities are independent of its RING finger domain. Furthermore, we found that CHFR physically interacts with p65 in cells. Electrophoretic mobility shift assays (EMSAs) and ELISA-based NF-jB-binding assays showed that CHFR negatively regulated transcriptional activity of p65. In addition, our data show that interleukin (IL)-8 is significantly downregulated by CHFR, and that the migration of human endothelial cells is suppressed in culture medium conditioned from CHFR-expressing cancer cells. Using a xenograft model, we show that neovascularization is suppressed by adenovirus-mediated transfer of CHFR. These results indicate that expression of CHFR markedly reduces the expression of IL-8 through the inhibition of NF-jB. As the NF-jB signaling pathway plays a critical role in the development and progression of cancer, our findings show the functional relationship between epigenetic alteration and inflammation/angiogenesis in human cancer cells, thereby showing several potential targets for therapeutic intervention.

show abstract

Section: Chfr Downregulates Nf-kb-dependent Transcriptionsupporting

confidence: 92%

CHFR, a potential tumor suppressor, downregulates interleukin-8 through the inhibition of NF-κB

et al. 2009

View full text Add to dashboard Cite

show abstract

“…In addition, different coactivators have been shown to regulate induction of different subsets of NF-B regulated genes. For example, we have previously shown that IRF3 and Bcl3 function as coactivator for induction of IP-10 but not MCP-1 in response to LPS and TNF␣ stimulation, respectively (22), while others have reported that RPS-3 is critical for induction of a subset of NF-B regulated genes upon TCR stimulation (23). Methylation of p65 may serve as direct or indirect interacting interface for recruiting these coactivators to form an enhanceosome to activate gene transcription.…”

Section: Discussionmentioning

confidence: 99%

Regulation of NF-κB activity through lysine monomethylation of p65

Kwee

Baltimore

2009

Proc. Natl. Acad. Sci. U.S.A.

202

181

View full text Add to dashboard Cite

NF-B is a key activator of inflammatory and immune responses with important pathological roles in cancer, heart disease, and autoimmune diseases. Transcriptional activity of NF-B is regulated by different posttranslational modifications. Here, we report a novel mechanism of NF-B regulation through lysine monomethylation by SET9 methyltransferase. Set9 specifically methylates p65 at lysine 37. Both TNF␣ and IL-1␤ treatments induced methylation of p65. Methylated p65 is restricted to the nucleus and this modification regulates the promoter binding of p65. Moreover, Set9 mediated methylation of p65 is required for the expression of a subset of NF-B target genes in response to TNF␣ stimulation.N F-B is a transcription factor that plays a pivotal role in regulating multiple biological functions including inflammation, immunity, cell proliferation, and apoptosis. NF-B represents a group of evolutionarily conserved and structurally related proteins. The 5 members of the mammalian NF-B, p65 (RelA), RelB, cRel, p50/p105 (NF-B1), and p52/p100 (NF-B2), form homo-or heterodimers that bind to I B family proteins in unstimulated cells (1). NF-B is sequestered in the cytoplasm through its interaction with the I B in resting cells. Stimulation of cells with a variety of ligands, such as tumor necrosis factor-␣ (TNF␣), interleukin-1␤ (IL-1␤), or pathogenassociated molecular patterns (PAMPs), leads to the rapid phosphorylation of I B by the I B kinase complex (IKK). The IKK kinase complex contains 2 catalytic subunits, IKK␣ and IKK␤, and the regulatory subunit, IKK␥. IKK catalyzes the phosphorylation of I B at 2 serine residues in the N terminus. The phosphorylated I B becomes ubiquitinated and subsequently degraded by 26S proteasome, thereby allowing NF-B to enter the nucleus to turn on a large array of target genes (1, 2).Although the activity of NF-B is regulated by nuclear translocation, covalent modifications of the protein by various events including phosphorylation, ubiquitination, nitrosylation, and acetylation can affect its activity (3). These regulatory modifications have distinct functional consequences. For example, acetylation of p65 at K218 and K221 inhibits I B␣ binding and enhances DNA-binding (4) whereas acetylation of p65 at K122 and K123 inhibits its transcriptional activating activity (5).Proteins can be posttranslationally methylated at lysine, arginine, histidine, and dicarboxylic amino acids by highly specific methyltransferases (6). In the process of protein-lysine methylation, the addition of methyl groups to the -amine of a lysine residue results in the formation of mono-, di-, or trimethyllysine. This process can be reversed by demethylases. Histone is one of the best studied proteins that undergoes methylation (7). Specific sites of methylation on histones correlate with either activation or repression of transcription. Recently, several transcription factors, including p53 (8, 9), STAT1 (10), RAR␣ (11), and ER␣ (12), have been shown to be methylated and their biological activity modified by the modif...

show abstract

“…S3 protein is involved in the synthesis of small ribosomal subunit (30S) and in the repair of DNA damage (Kim et al 2005). S3 may also function as a transcription factor (Wan et al 2007). In connection with these functions, this protein may cause an increase in triticale stress tolerance.…”

Section: Discussionmentioning

confidence: 99%

Changes in the root proteome of Triticosecale grains germinating under osmotic stress

2013

View full text Add to dashboard Cite

Osmotic stress causes many adverse symptoms in plants, which include, for example, growth limitation and decrease or even absence of yield. Proteomic analyses of plant responses to stressors could lead to the introduction of crops with high resistance to osmotic stress. Such plants would be characterized by high yield even under unfavorable environmental conditions. In this article we describe changes in the protein profiles occurring in response to mild and moderate osmotic stress in triticale roots. Analysis of the protein profiles of these roots showed an increased abundance of 14 and a decreased abundance of 11 proteins under mild osmotic stress conditions while a moderate osmotic stress caused an increased abundance of 18 and a decreased abundance of 33 proteins. Twenty-five proteins, whose quantity altered under stress were identified using MALDI-TOF mass spectrometry. The identified proteins were classified into the categories of proteins associated with: defense mechanisms, metabolism, transcription, cell structure, protein synthesis, transport and signal transduction. The functions of identified proteins were discussed in relation to osmotic stress. Some of the identified proteins may be responsible for the adaptation of plants to adverse conditions.

show abstract

Ribosomal Protein S3: A KH Domain Subunit in NF-κB Complexes that Mediates Selective Gene Regulation

Cited by 311 publications

References 35 publications

CHFR, a potential tumor suppressor, downregulates interleukin-8 through the inhibition of NF-κB

CHFR, a potential tumor suppressor, downregulates interleukin-8 through the inhibition of NF-κB

Regulation of NF-κB activity through lysine monomethylation of p65

Changes in the root proteome of Triticosecale grains germinating under osmotic stress

Contact Info

Product

Resources

About