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Fine Effort but some missing citations[edit]

This is a very fine effort about one of the increasingly important molecular players implicated in cancer, inflammatory processes, and a host of other cell signaling issues. However, I think you have not cited one of the key researchers (Bharat Aggarwal at the University of Texas). He has dozens of papers on this issue, looking specifically at phytochemical regulation of NF Kappa B. see,+Bharat+B[Full+Author+Name] for a full listing. DFW Harvard Medical School —Preceding unsigned comment added by (talk) 14:37, 12 September 2008 (UTC)

Thanks for your note. Aggarwal certainly has published a lot of papers about NF-κB, but his interest seems mainly restricted (and nothing wrong with that) to NF-κB role in disease and the potential therapeutic applications. I have therefore expanded the NF-κB#NF-.CE.BAB_as_a_drug_target section and included to citation to recent review write by Aggarwal. I hope this is sufficient. Cheers. Boghog2 (talk) 12:53, 14 September 2008 (UTC)


This article is about NF-kB yet there is no information on the MW, the amino acid sequence, the topology of the protein, if it is a functional homodimer. I think articles about proteins should address these.

I agree with you that topology/structure should be included therefore I have added a new schematic figure which I hope addresses this need. Also I agree that information about whether these proteins function as homo- or heterodimers should be included. I am not an expert on NF-kB, but from what I have read, it appears that both are biologically relevant. Concerning the MW, the p50, p52, etc. protein names denote their MW in kDa (50 and 52 kDa respectively). However given the amount of post translational modification and between individual variation in sequence, exact MWs of proteins this size in my opinion are not that relevant. Finally, links to the protein sequences may be found to the right in the protein boxes. Including sequence directly in the article, especially in an article about a family of proteins is again, in my opinion, not that useful. The links should be adequate. Cheers. Boghog2 21:36, 6 November 2007 (UTC)

Also it is mentioned that NF-kB's role in the CNS is controlversial but no references are provided on this point one way or the other.


Question - Is there a tumor with NF-KB and Ubiquitin affected?

I'm not sure what you mean, can you be more specific? By "Ubiquitin" do you mean the protein or the pathway?

Also, in your section on NF-kB and cancer, you state, "When NF-κB becomes mutated such that the cell proliferation pathway is constitutively activated, the cells in which NF-κB is mutated may readily spiral down into uncontrolled proliferation, a hallmark of tumors." While it's possible this happens in some cases (though I'm not aware of any), the typical case is that NF-kB family members are amplified or rearranged; while one could think of these as mutations, we typically don't, we think of them as amplification and rearrangement. NF-kB signaling can also be upregulated by oncogenes, the classic case being Ras and Raf (though I can't recall the reference). Another well-known oncogene is Her2/Neu, a significant player in breast cancer, which activates Akt, leading to activation of NF-kB-dependent gene expression. There may also be a role for IkB inhibition in the upregulation of NF-kB in cancer, but nothing specific comes to mind.

All that said, this is a tough article to write, and you've done a great job--much better than I could have done. :) ~Doc~ EquationDoc 04:05, 12 November 2006 (UTC)

Unspecific references[edit]

I moved the following refereneces, that doesn't seem to be cited in the main text. Please reintroduce them if appropriate...:

[1] Shehata M, Rel/Nuclear factor-kappaB apoptosis pathways in human cervical cancer cells, Cancer Cell International 2005, 5; 10.

[2] Lindström MT, Bennet R Philip, The role of nuclear factor kappaB in human labor. Reproduction (2005) 130: 569-581.

[3] Buss H, Dörrie A, Schmitz M, Lienhard M, Hoffman E, Resh K, Constitutive and Interleukin-1-inducible Phosphoryltion of p65 NF-κB at Serine 536 Is Mediated by Multiple Protein Kinases Including IκB Kinase (IKK)-α ,IKKβ, IKKЄ, TRAF Family Member-associated (TANK)-binding Kinase 1 (TBK1), and an Unknown Kinase and Couples p65 to TATA-binding Protein-associated Factor II31-mediated Interleukin-8 Transcription. Journal of Biological Chemistry 2000; 279 (53): 55633-55643.

[4] Barnes, Peter J., Karin, Michael. Nuclear Factor-κB -- A Pivotal Transcription Factor in Chronic Inflammatory Diseases. New England Journal of Medicine 1997; 336: 1066-1071

[5] Gilmore, Thomas D. (editor). NF-κB: From Basic Research to Human Disease. Oncogene Oct 2006; 25 (51): 6679 - 6899

Kjaergaard 09:35, 21 January 2007 (UTC)


I have moved the mechanism and structure figures back to the top of the page for the following reasons:

  • In the Safari web browser for some browser window widths, the [previous] graphic placement resulted in some of the text being hidden behind the graphic. In Firefox, unless the browser window width was set very wide, the previous placement caused the references section to be compressed to a very narrow and almost unreadable column width.
  • In the [previous] version, the structure figure was displayed next to the references. In the [current] version, the structure graphic (depending on the width of the web browser window) is displayed next to or very near the structure section.
  • I understood the logic for placing the graphics in the "Activation of NF-κB" section in the raw wiki text. However because of the large number of protein boxes, the graphic in the final rendered form of the article ended up being displayed considerably below this section and therefore the reader may not be aware that the figure exists when reading the corresponding mechanism section text. As it stands now, the mechanism graphic is above the mechanism section of the text, but once the reader reaches the mechanism text, the reader will remember seeing the graphic and can refer back it.

Cheers. Boghog2 06:30, 13 November 2007 (UTC)

hey hey hey[edit]

I know bupkis about molecular biology but NF-whatever is in the news: —Preceding unsigned comment added by Foogus (talkcontribs) 04:50, 3 December 2007 (UTC)


I thought there was no single NF-kB. Several members of the family can associate to form a functional dimer, which is not limited to p50 with p52 (e.g., p50 and p65 also exist, other dimers with RelA (=p65), c-Rel, RelB, etc.). In fact the so-called 'canonical' pathway involves p65 associated with p50, and not p50 + p52. Jack the Stripper (talk) 17:18, 5 March 2008 (UTC)

I.e. not as implied here: In contrast, the NF-κB1 and NF-κB2 proteins are synthesized as large precursors, p105, and p100, which undergo processing to generate the mature NF-κB subunits, p50 and p52, respectively. Jack the Stripper (talk) 17:20, 5 March 2008 (UTC)


I propose that this article be reorganized slightly to make it more generally accessible and to mirror the format of many NF-κB reviews. It might be helpful if "Inhibitors of NF-κB" are discussed earlier, at least before "Activation of NF-κB." (Many reviews include the IκB proteins in the list of NF-κB family members.) I would also like to remove some of the information from protein boxes (some are redundant while others contain little information) to clean the page up a bit.

If there are no objections, I would like to begin making some of these changes. Jacchigua (talk) 16:23, 19 May 2008 (UTC)

Hi Jacchigua. Your proposed reorganization sounds reasonable. However I don't understand your comment concerning the protein boxes. Which information is redundant and/or contains little information? Perhaps the protein/gene names which are based on the official HUGO gene names could be abbreviated which would make the boxes look cleaner. Cheers. Boghog2 (talk) 16:46, 19 May 2008 (UTC)
Hey Boghog2. I thought that a couple of the protein boxes were duplicates lacking structures, but now I see that I got lost in the HUGO gene names and that there is a box for each protein discussed in the article. Abbreviating the HUGO names to the more common names used in the article is about all I would change with the protein boxes. I've been watching this article for a while and it is looking nice. Thanks! Jacchigua (talk) 18:27, 19 May 2008 (UTC)

NF-κB's role in cancer and other diseases[edit]

You have the following line in this section: "Defects in NF-κB results in increased susceptibility to apoptosis leading to increased cell death." The way I'm reading this, I'm not sure if by defects you are referring to activation or inactivation or NF-kB. Activation of NF-kB leads to up-regulation of anti-apoptosis mechanisms thus making the cell less suceptable to apoptosis and cancer chemotherapy. I think you may need to clarify this a bit. —Preceding unsigned comment added by Zaxtrax (talkcontribs) 12:57, 7 August 2008 (UTC)

I agree. This has confused me! — Preceding unsigned comment added by (talk) 14:08, 27 May 2012 (UTC)

Suppression by glucocorticoids?[edit]

Nothing on suppression by glucocorticoids?
Science 13 October 1995:
Vol. 270. no. 5234, pp. 286 - 290
DOI: 10.1126/science.270.5234.286
Reports: Immunosuppression by Glucocorticoids: Inhibition of NF-B Activity Through Induction of IB Synthesis
Nathalie Auphan, Joseph A. DiDonato, Caridad Rosette, Arno Helmberg, Michael Karin
N Engl J Med. 2005 Oct 20;353(16):1711-23.
Antiinflammatory action of glucocorticoids--new mechanisms for old drugs.
Rhen T, Cidlowski JA.
Department of Biology, University of North Dakota, Grand Forks, USA.
PMID: 16236742 [PubMed - indexed for MEDLINE]

My understanding is that NF-κB is the target when glucocorticoids are used to control inflammation, and in larger doses when used to control cancer. Right? Or how would you phrase it? --Nbauman (talk) 21:26, 20 December 2009 (UTC)

NF-κB is only one of a large number of targets that glucocorticoids act through to control inflammation. The primary target of almost all the anti-inflammatory of effects of glucocorticoids (GCs) is the glucocorticoid receptor (GR). Activated GR upregulates the expression of IκBα which in turn inhibits NF-κB (Auphan et al.) Furthermore when GR is activated by GCs, NF-κB in turn is deactivated by GR through a process known as transrepression. In addition to NF-κB, several other transcription factors such as AP-1 are transrepressed by activated GR. Boghog (talk) 04:11, 21 December 2009 (UTC)
NF-κB is one of the targets, but doesn't glucorticoid act primarily on the NF-κB pathway? From what you're saying, the GR is on the NF-κB pathway, as I understand it. Right? --User:Nbauman|Nbauman]] (talk) 17:30, 21 December 2009 (UTC)
While the NF-κB pathway certainly plays an important role in mediating GCs anti-inflammatory response, to say that GCs act primarily through the NF-κB pathway to control inflammation is misleading (see PMID 17622575 for a good recent review). Other pathways independent of NF-κB are also effected and these other pathways collectively are at least if not more important than the NF-κB pathway. It would be more accurate to say "glucorticoids act in part through the NF-κB pathway to mediate their anti-inflammatory effects". Boghog (talk) 20:34, 21 December 2009 (UTC)


Is rel homology domain a kind of DNA binding domain? 16:20, 12 October 2010

According to the rel homology domain article, this domain certainly seems to fulfill the requirements of a DNA-binding domain (i.e., a protein domain that binds DNA). Boghog (talk) 18:43, 12 October 2010 (UTC)

NF-kB and Inflammation: "incorrect regulation" or main effect?[edit]

The article states:

  • "Incorrect regulation of NF-κB has been linked to cancer, inflammatory and autoimmune diseases, septic shock, viral infection, and improper immune development."

However, IMHO, local inflammation is a direct effect of activation of NF-kB pathway in a given cell, tissue, or organ. Cynthesis of cytokines (IL-1b, TNF, IL-6), fever, specific changes in macrophages/monocytes, neutrophils, endothelium - if we take the cellular effects, they would be identical to inflammation. I guess that instead of "incorrect regulation" we should write something like:

  • "NF-kB pathway is a key participant in inflammatory responses to pathogens and alarmins (or PAMP/DAMP). Persistent or generalized activation of NF-kB leads to inflammatory diseases and septic shock; incorrect regulation of NF-kB has been linked to cancer, autoimmune diseases, and improper imm. dev."

--Indeed, from the original phrase it is not clear what "correct" regulation of NF-kB. By logic of the orig. phrase the only "correct" regulation would be NO activation, silence :).

Agreed. Also "dysregulation" would probably be a better term than "incorrect regulation". Boghog (talk) 11:34, 12 December 2012 (UTC)

Poorly cited information about specific genes putatively regulated by NF-κB, "In the nervous system"[edit]

Under the "In the nervous system," I would recommend removal of the citations about regulation of expression of neurotransmitter receptors and PSD-95. I have looked carefully at these papers, and none was found to test regulation of these genes in the appropriate cell type (neurons). Ref #43 was completely devoid of any mention of NF-κB; #44 used a tumor-derived cell line rather than neurons and performed no antibody supershifts or other techniques to identify the binding activity appearing on EMSA; #45 was a report of DNA sequence alone (and one capable of regulation by Sp1-family factors at that); #46 reported only a polymorphism that showed weak linkage to a disease state, with no functional tests of transcriptional effect (indeed, the G-->C change in the first position in a 'GGGG...' consensus sequence would not be expected to diminish NF-κB binding). Ref #41, concerning PSD-95, included no promoter analysis or other tests of a direct role for NF-κB in the cells actually expressing the gene product (not to mention that the culture technique described will certainly include a considerable number of glia). Neuroglider (talk) 03:50, 23 November 2013 (UTC)

Thanks for your careful analysis and for your contributions to the article. Based on what you have said above, I would support removal of the citations that you mention and any associated text whose only support are these citations. Boghog (talk) 09:22, 23 November 2013 (UTC)

NEMO deficiency syndrome[edit]

Following a question over on the Wikipedia Science Reference desk, it appears that Wikipedia does not have any information whatever about "NEMO" (Nuclear factor-kappa B Essential MOdulator deficiency syndrome) - which, AFAICT, is a rare genetic condition related to a faulty NF-kB gene. I added a stub article using information from Great Ormond Street Childrens' Hospital - and added a section here to offer a brief description and a link to it.

However, this is far outside my field of expertise and I hope someone here could take some time to pick up that stub article and improve on it.

Right now, it's a separate stub article - but if the feeling was that the encyclopedia would be better served with just a link into a section of this article, then I'd be fine with that...but the total lack of coverage of NEMO in Wikipedia needed fixing, so I decided to "Be Bold".  :-)

TIA SteveBaker (talk) 18:50, 25 June 2016 (UTC)

Thanks for creating the stub. It appear though that the syndrome is not due to a deficiency of NF-κB, but rather IKBKG (aka NEMO) that in turn activates NF-κB. Boghog (talk) 22:13, 25 June 2016 (UTC)