Talk:Aryl hydrocarbon receptor

Ligand Updating

Hey so some of the information on this page may be outdated, it says that the identity of the endogenous ligand to this receptor is currently not known. I know of one such ligand, 2-(1′H-indole-3′-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE). Here's the article that describes its discovery: http://www.pnas.org/content/early/2010/11/09/1009201107 Here's another article talking about it's use in Nanoparticles: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3396465/ Hopefully someone can go about fixing this issue, I would do it myself but I'm currently doing a project, so I don't have the time. I also don't really wanna go about fixing it and doing it incorrectly. Quite honestly, I really just don't have time to do the citations, but here's the abstract for the first article: An endogenous aryl hydrocarbon receptor ligand acts on dendritic cells and T cells to suppress experimental autoimmune encephalomyelitis The ligand-activated transcription factor aryl hydrocarbon receptor (AHR) participates in the differentiation of FoxP3+ Treg, Tr1 cells, and IL-17–producing T cells (Th17). Most of our understanding on the role of AHR on the FoxP3+ Treg compartment results from studies using the toxic synthetic chemical 2,3,7,8-tetrachlorodibenzo-p-dioxin. Thus, the physiological relevance of AHR signaling on FoxP3+ Treg in vivo is unclear. We studied mice that carry a GFP reporter in the endogenous foxp3 locus and a mutated AHR protein with reduced affinity for its ligands, and found that AHR signaling participates in the differentiation of FoxP3+ Treg in vivo. Moreover, we found that treatment with the endogenous AHR ligand 2-(1′H-indole-3′-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) given parenterally or orally induces FoxP3+ Treg that suppress experimental autoimmune encephalomyelitis. ITE acts not only on T cells, but also directly on dendritic cells to induce tolerogenic dendritic cells that support FoxP3+ Treg differentiation in a retinoic acid-dependent manner. Thus, our work demonstrates that the endogenous AHR ligand ITE promotes the induction of active immunologic tolerance by direct effects on dendritic and T cells, and identifies nontoxic endogenous AHR ligands as potential unique compounds for the treatment of autoimmune disorders. — Preceding unsigned comment added by 98.118.113.138 (talk) 00:05, 7 April 2013 (UTC)

Initial Comments

I'm sorry, I have no information, I just seriously could not understand a word of that. And I'm pretty good at Chemistry... and Biology. — riana_dzasta _{wreak havoc|damage report} 06:00, 14 September 2006 (UTC)

That's fine. Can you give us some more information on what it is that is confusing? Do you understand the basics of transcription factors (see the linked TF article)? I realize there is a lot of jargon in the article, so maybe that turned you off. But recognize that it is a farily specific protein that is studied only by a few people, so I am not sure how non-techncial the article needs to be. What brought you to the article? Biomedeng 01:27, 30 September 2006 (UTC)

Wow, you know what, this is embarrassing, but I think I tagged the article very late at night when my brain was able to process very little information. As for what brought me here, I think I was removing links to a disambiguation page, and looked at this article and couldn't understand a word. I totally understand now, it's hard to baby these down too much without losing information. My apologies if that was bothering you - I'm removing the tag now :) riana_dzasta 05:14, 26 November 2006 (UTC)

Major Editing Needed

Will get started on it shortly. Demantos 17:44, 11 May 2007 (UTC)

UB. Worked on the Protein Structure Section. Will work on others later. Demantos 18:32, 11 May 2007 (UTC)

Have potential subcategories defined. Demantos 19:28, 11 May 2007 (UTC)

Still working on image copyrights. Demantos 19:28, 11 May 2007 (UTC)

UB. Added section pertaining to signaling pathway. Still looking for a good figure to illustrate. Demantos 13:42, 15 May 2007 (UTC) UB. Still cleaning up. Will work on ligands section later. Demantos 15:53, 15 May 2007 (UTC)

UB. Updated the references to the standardized approach. Demantos 15:47, 16 May 2007 (UTC)

Thanks for your hard work and dilligent referencing on the article. This is a tremendous improvement and I think the article may be getting close to B status. I can probably add a fair amount to the ligands section, in particular for endogenous ligands. One concern I have is that the new images on the article are from copyrighted journal articles. Are you an author of either of these articles? If not how did you go about getting permission? Biomedeng 00:59, 18 May 2007 (UTC)

UB. I am working on getting the Permissions now. I have permission from Annual Reviews for Image #2 and am waiting to hear back for image #1. I am not sure how to classify the images so that may need to be changed by someone who knows more. To obtain permissions, I have contacted the copyright office of each journal. Demantos 11:40, 29 May 2007 (UTC)

Image Permissions

UB. All permissions have been obtained for the two images currently displayed. Written permission was obtained from the journals copyright administrator with the understanding that permission would be expressed within the figure legend. Demantos 18:38, 29 May 2007 (UTC)

When adding references

Please use this tool to keep all references standardized. http://diberri.dyndns.org/wikipedia/templates/ Make sure to check the ADD ref tag box. Demantos 11:40, 29 May 2007 (UTC)

Merge content from Xenobiotic Response Element

Demantos 18:40, 26 August 2007 (UTC)

Still working

Now that I have some more time, I'm still working on the page UB. Demantos 13:39, 7 November 2007 (UTC)

Peer review

Since I am not sure I can get around to it soon, here are the results of the peer review Demantos (talk) 15:50, 3 January 2008 (UTC)

Review by Jeff

A good start: the facts are here and the refs are very thorough. Rewriting (not just punctuation and spelling) will improve the article significantly.

• The article should put information into context better, so that the average reader can understand what is going on. For example:

• "Non-ligand bound Ahr is retained in the cytoplasm as an inactive protein complex consisting of a dimer of Hsp90 " the phrase 'Non-ligand bound' is incomprehensible to the average reader, but if I write:
• "When no ligands of the receptor are present, Ahr is retained in the cytoplasm as an inactive protein complex...When a ligand enters the cell and binds to the receptor, this inactive protein complex dissociates, allowing importation of the receptor into the nucleus so that it can interact with the cell's DNA."
• This sentence can be the lead of the paragraph or section, after which you can discuss the details. The idea is to tell the big story first so we can understand it in context, and only then can you explain the details.

• This receptor is responsible for activating the body's response to xenobiotics, right? So this should be explained clearly in the lead.
• The opening sentence is: "The Aryl hydrocarbon receptor (AhR) is a member of the family of basic-helix-loop-helix transcription factors." Is this really the most important thing about this protein, and does it help explain the essence of the receptor to a casual reader? Consider replacing with the suggestion above.
• The lead should summarize all important aspects of the receptor, such as who discovered it and when, what the receptor's purpose is, and why scientists are still researching it.
• There is a problem with licensing of Image:AhR.jpg. This has a half-written fair use rationale, but a free version can be made! We can't have fair-use material if free versions can be made. In fact, I will volunteer to make a free version of this, but I'm going to tag the existing version as a copyvio. ("reprinted with permission" where is the documentation? What is the permission given, and who gave it? if permission really has been given, should have an OTRS ticket). As for Image:AhRSignaling colour.png, I'm not entirely happy since it is almost an exact re-drawing of the original and a free version could easily be made. I'm not quite sure what to do with that one, so I'll leave it alone for now.
  • • • I was given journal permission via email for the images used in the article. Demantos (talk) 16:01, 3 January 2008 (UTC)
• Are there any crystal structures available? How about any structures or models of any of the binding domains? I can access Sybyl and Chem3D for rendering structures if coordinates or other structure information is available.
  • • • Ahr has not been crystalized Demantos (talk) 16:01, 3 January 2008 (UTC)
• Abbreviations: I recommend not using abbreviations unless you really need them, so if you only use a term once or twice, why bother abbreviating? Abbreviations are very hard to read, and make the article look like an alphabet soup. On the other hand, there are things than should not be spelled out, such as CYP1A1, Hsp90, XAP2. Just say: "...the metabolic enzyme CYP1A1..." (no need to say "cytochrome P450, family 1, subfamily A, polypeptide 1" or spell them all out). The choice of what words to spell out should be made carefully.
  • • • Currently only gene names are abbreviated Demantos (talk) 16:01, 3 January 2008 (UTC)
• Abbreviations: Even more annoying than an unnecessary abbreviation is re-defining the abbreviation over and over: "...aryl hydrocarbon receptor nuclear translocator(ARNT)..." and later "...AhR Nuclear Transporter (ARNT)..." (note inconsistency) Why say it more than once? Clunky abbreviations are a pet peeve of mine in journal articles, so I'm sorry if this sounds terse. For ARNT I would suggest saying: "...AhR's dimerization partner, a nuclear transporter called ARNT." Also use consistent CAPS on AhR or Ahr.
• "...the end result is a variety of differential changes in gene expression." add perhaps 2 sentences summarizing what these changes are.
• Avoid sentences like "reviewed by^[8][9]." and "as shown in^{[52][53][54][46]}." (don't use a footnote as the object of a sentence!) and the period should come before the refs.
  • • • Fixed Demantos (talk) 16:01, 3 January 2008 (UTC)
• I hope I don't sound too harsh; I don't mean it to be. The article needs some rewriting so that non-experts can read it, but the content and refs are good. I would suggest one more image, if possible, would be a structure or model of the receptor, or at least one of the subdomains. And perhaps a structure of a typical aryl hydrocarbon with a caption like "Polychlorinated dibenzodioxins such as TCDD activate the aryl hydrocarbon receptor, activating the xenobiotic response element" I'm happy to answer more questions, take another look, and help out if I have time. Jeff Dahl (Talk • contribs) 22:00, 4 December 2007 (UTC)

• A script has been used to generate a semi-automated review of the article for issues relating to grammar and house style. If you would find such a review helpful, please click here. Thanks, APR _t 19:44, 5 December 2007 (UTC)

• Nice work. 1) The lead needs to be made accessible to non specialists. It's a detailed topic, so the whole article doesn't need to be accessible, but the lead section should be maximally so. The first sentence "Aryl hydrocarbon receptor (AhR) is a member of the family of basic-helix-loop-helix transcription factors." tells me absolutely nothing about the topic, and I have a fair amount of science background. The next sentence and the rest of the lead don't provide much more; it's not until the very last two words that I can tell what the topic is related to. Luckily the article is short, so there is a fair amount of room to add context here and there. Particularly in the lead you should minimize the use of overly complicated terms where possible, and define them in context when not. For example I can read the Transcription factor article to find out in general what AhR is, but in general the reader shouldn't have to. Also the lead section should be 2 or 3 paragraphs, see WP:LEAD. 2) In all that research, which is impressive by the way, would you say there are no other important bits of material you have left out? Without references and markup it's pretty short for a featured article candidate. - Taxman ^Talk 19:29, 6 December 2007 (UTC)

Correction needed? - Is a receptor a transcription factor? That seems wrong.

The first paragraph states:

"The Aryl hydrocarbon receptor (AhR or AHR) is a member of the family of basic-helix-loop-helix transcription factors. AhR is a cytosolic transcription factor that is normally inactive, bound to several co-chaperones."

Is it not true that a transcription factor is a PROTEIN that BINDS to a RECEPTOR? If so, then why is the receptor referred to as BEING the transcription factor? It seems that this must be a mistake. 208.54.94.8 (talk) 17:06, 14 March 2009 (UTC)

=== A receptor binds a LIGAND which can be anything from a protein to a small molecule to a drug, etc. Ligands bind to AHR which then activate the protein and cause it and ARNT to bind DNA causing changes in transcription. Transcription factors bind to DNA. It has been estabilshed for over 30 years that AHR is a transcription factor. This is a basic concept in cell biology, please refer to an appropriate text book.Demantos (talk)

=== It most certainly is a TF, this paper here describes its binding to cyp1a1 gene: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3396465/ — Preceding unsigned comment added by 98.118.113.138 (talk) 00:00, 7 April 2013 (UTC)

AHR and smoke

In a study published on early August 2016, AHR's presence in homo sapiens sapiens has provided this branch a much lesser susceptibility to smoke-induced diseases caused by (fireside) smoke — compared to Neanderthals and the Denisova[n] branch, who did not have AHR. This may have given a genetic advantage to what became the modern human. Article in The Guardian here. -Mardus /talk 11:01, 28 September 2016 (UTC)

Too technical

All I did was add a space, because I don't know how to ask the question, "Isn't Wikipedia supposed to be for EVERYONE to use?" Anyone who would understand this entry CLEARLY does not need to read Wikipedia for their information, since they've probably already got a PhD in organic chemistry or something. This reads like a journal article or a graduate school textbook and assumes either a VAST amount of pre-existing knowledge or a really hardcore level of motivation (to go after every linked...) 207.138.216.85

I copied the aboved comment from this edit as I thought it was very appropriate. I edited the lead to try to make a little bit less technical. I hope this is an improvement. Boghog (talk) 19:18, 5 September 2018 (UTC)