Talk:2012 Group 5 Project

From CellBiology
Revision as of 15:37, 10 May 2012 by Z3289738 (talk | contribs)

--Mark Hill 11:46, 4 April 2012 (EST) As of Wed 4th April (week 5) other than the requested individual assessment references there is nothing on your project page (except the template sub-headings) or discussion page (other than allocation of work) that indicates that you are carrying out the research work on your project . I remind you of the assessment criteria and my expectation of ongoing demonstrable contributions.

  • The key points relating to the topic that your group was allocated are clearly described.
  • The choice of content, headings and sub-headings, diagrams, tables, graphs show a good understanding of the topic area.
  • Content is correctly cited and referenced.
  • The wiki has an element of teaching at a peer level using the student’s own innovative diagrams, tables or figures and/or using interesting examples or explanations.
  • Evidence of significant research relating to basic and applied sciences that goes beyond the formal teaching activities.
  • Relates the topics and content of the Wiki entry to learning aims of cell biology.
  • Clearly reflects on editing/feedback from group peers and articulates how the Wiki could be improved (or not) based on peer comments/feedback. Demonstrates an ability to review own work when criticised in an open edited wiki format. Reflects on what was learned from the process of editing a peer’s wiki.
  • Evaluates own performance and that of group peers to give a rounded summary of this wiki process in terms of group effort and achievement.
  • The content of the wiki should demonstrate to the reader that your group has researched adequately on this topic and covered the key areas necessary to inform your peers in their learning.
  • Develops and edits the wiki entries in accordance with this sites wiki guidelines.

Group 5's Discussion Board

Hey, I found a list of areas for future research in my article so I copied it over to that section.

Its looking good guys :)

--Z3289738 15:37, 10 May 2012 (EST)

Hey guys, I was also having issues uploading things onto the wiki, everytime I edited something it would save and then disappear - very frustrating! Everythings up now so hopefully it will stay there.

As for everything below I just needed to paste it somewhere while I edit it further


Wnt/β-Catenin Signaling: Components, Mechanisms, and Diseases [1]

  • Signaling by the Wnt family of secreted glycolipoproteins is one of the fundamental mechanisms that direct cell proliferation, cell polarity, and cell fate determination during embryonic development and tissue homeostasis (Logan and Nusse, 2004). As a result, mutations in the Wnt pathway are often linked to human birth defects, cancer, and other diseases (Clevers, 2006). A critical and heavily studied Wnt pathway is the canonical Wnt pathway, which functions by regulating the amount of the transcriptional coactivator β-catenin, which controls key developmental gene expression programs.
  • Given the critical roles of Wnt/b-catenin signaling in development and homeostasis, it is no surprise that mutations of the Wnt pathway components are associated with many hereditary disorders, cancer, and other diseases (Table 1).
  • Association of deregulated Wnt/β-catenin signaling with cancer has been well documented, particularly with colorectal cancer (Polakis, 2007) (Table 1). Constitutively activated β-catenin signaling, due to APC deficiency or β-catenin mutations that prevent its degradation, leads to excessive stem cell renewal/proliferation that predisposes cells to tumorigenesis.
  • Mutations of β-catenin at and surrounding these serine and threonine residues are frequently found in cancers, generating mutant β-catenin that escapes phosphorylation and degradation (Table 1).

Caught up in a Wnt storm: Wnt signaling in cancer [2]

  • The Wnt signaling pathway, named for its most upstream ligands, the Wnts, is involved in various differentiation events during embryonic development and leads to tumor formation when aberrantly activated. Molecular studies have pinpointed activating mutations of the Wnt signaling pathway as the cause of approximately 90% of colorectal cancer (CRC), and somewhat less frequently in cancers at other sites, such as hepatocellular carcinoma (HCC).
  • Greater than 90% of all CRCs will have an activating mutation of the canonical Wnt signaling pathway, ultimately leading to the stabilization and accumulation of β-catenin in the nucleus of a cell.
  • Fig. Schematic representation of a colon crypt and proposed model for polyp formation. At the bottom third of the crypt, the progenitor proliferating cells accumulate nuclear β-catenin. Consequently, they express β-catenin/TCF target genes. An uncharacterized source of WNT factors likely resides in the mesenchymal cells surrounding the bottom of the crypt, depicted in red. As the cells reach the mid-crypt region, β-catenin/TCF activity is downregulated and this results in cell cycle arrest and differentiation. Cells undergoing mutation in APC or β-catenin become independent of the physiological signals controlling β-catenin/TCF activity. As a consequence, they continue to behave as crypt progenitor cells in the surface epithelium giving rise to aberrant crypt foci.

--Z3289738 11:22, 10 May 2012 (EST)

Hey guys, really sorry but I don't know what happened to the last bit of our wiki page! >.< I was still adding to the glossary this morning, and I just went back to check out our page, and now it's missing!! I've tried undoing a few things but it hasn't come back...

I actually have to leave home for class now, and I won't be free right up until the lab begins (when the page will most likely be locked). I'm really sorry to ask the favour, but could someone please figure out how to bring back the lost data? I haven't kept an offline copy of the current/future research and glossary (and everything else beyond it)...

What I did do, however, is keep an offline copy of my table for the key players. I'll paste it here; could someone update my section by just copy pasting this chunk under "key players in signalling" and remove all other content under that heading? Thanks in advance and sorry again. Have to go now.

Protein (Gene) Structure Function Inhibitors
Wnt (WNT) Structure of beta-catenin.JPG

Evolutionarily conserved protein across species [3]. Most Wnt proteins figure in the region of 40 kDa, each possessing a characteristic 23 or 24 cysteine residues highly conserved in their spacing. This suggests that the formation of disulfide bonds plays a significant role in determining tertiary protein structure [4].

Initiates Wnt signalling when it binds as a ligand to the Fz receptor with LRP [5]and destabilises the β-catenin degradation complex, dephosphorylating β-catenin and subsequently enabling its migration and accumulation in the cell nucleus for gene transcription [2].
  • The FRP family resembles the Wnt-interacting domain of Fz receptors, thus competitvely sequesters Wnt from the Fz receptor [6].
  • WIF-1 has been shown to competitively antagonise Wnt binding to the Fz receptor [7].
  • Cerberus is a secreted protein that directly binds to the Wnt protein and inhibits signal transduction [8]
  • Dkk indirectly inhibits Wnt protein signalling by binding to the co-receptor LRP-6, thus making it unable to bind to Wnt for Fz signal transduction [9].
  • The extracellular sFRP family of proteins possess a consensus CRD sequence on their N-terminus, with which they directly bind to Wnt, and prevent its association with Fz receptors, thus antagonising the signal conduction [10].
  • Experiments suggest that axin indirectly blocks Wnt signalling, in a manner that renders further increases in Wnt levels ineffective [11]
Fz (FZD) Frizzled.png
Fz houses a CRD on the N-terminus, seven transmembrane domains, and a PDZ domain on the C-terminus [4]
Binds the Wnt ligand at the extracellular N-terminus for the initiation of the Wnt/β-catenin signalling pathway [4]
LRP-5/6 (LRP) LRP1.png

A protein that spans multiple domains. The extracellular component is comprised of four EGF-like repeats on the N-terminus [9].

Co-receptor to the Wnt ligand in its interaction with the Fz receptor in signal transduction [12]. Causes translocation and association of axin to its intracellular tail, thus destabilising the β-catenin binding activity of axin [13].
  • Dkk antagonises LRP-5/6 binding to Wnt through competitive binding [9] and complexes with the transmembrane protein Kremen2 for intracellular removal cell through endocytosis [14].
Dsh (DVL) Dsh.jpg Prevents phosphorylatory activity of GSK-3β upon hyperphosphorylation by the Wnt/LRP-5/6 complex binding to the Fz receptor[15], thus preventing β-catenin ubiquitination and degradation, to promote translocation into the nucleus.
  • Nkd blocks feedback signalling, thus inhibiting Dsh [16]
  • Stbm binds to and jointly immunoprecipitates Dsh [17]
  • Dapper antagonises Dsh in complex with Axin, GSK-3β, CK-I and β-catenin, leading to degradation of β-catenin and subsequent reduced signalling [18]
  • PKC, a serine/threonine-specific protein kinase product of the non-canonical Wnt/Ca2+ pathway, inhibits Dsh through phosphorylation, preventing β-catenin nuclear translocation [19]
  • Experiments suggest that axin indirectly blocks Dsh function, in a manner that renders further increases in Dsh levels ineffective [11]
Axin (AXIN) AXIN1.png In the absence of Wnt signalling, it constitutes the β-catenin ubiquitination complex along with APC and GSK-3β [5]and its role as a scaffolding protein enhances GSK-3β phosphorylation of β-catenin [20].
  • Wnt downregulates axin through increased Dsh expression, hindering axin phosphorylation by GSK-3b, leading to decreased stability and ultimately a shorter half-life [21]
GSK-3β (GSK3β) GSK3B.png Constitutes the β-catenin ubiquitination complex along with axin and APC [5]; its primary role in the Wnt/β-catenin signalling pathway is inhibition of β-catenin nuclear translocation through phosphorylation of three amino acids at the N-terminus [22] after priming by CK-1 [23], for subsequent ubiquitination and degradation by the proteasome. This activity is enhanced by GSK-3β phosphorylation of axin [20] and APC [24] which appears to promote phosphorylation of β-catenin by GSK-3β in the complex.
  • Frat1, which appears to be recruited by Dsh in complex, tightly binds GSK-3b even after complex dissociation and b-catenin degradation [25]
  • PKC inhibits GSK-3β phosphorylatory activity [26]
Diversin Primes b-catenin for degradation by recruiting CK-I to phosphorylate serine 45 on the N-terminus before subsequent phosphorylation of threonine 41, serine 37 and serine 33 by GSK-b and degradation by E3 ubiquitin ligase β-TrCP [23]
APC (APC) Structure APC.jpg

A large 312 kDa protein.

Possesses a numerous and varied set of roles ranging from cell migration and adhesion, cell cycle regulation and chromosome stability [PMID: 11978510][27]. In the Wnt/β-catenin signalling pathway, APC constitutes the β-catenin ubiquitination complex along with axin and GSK-3β [5]. It binds to axin via SAMP elements [28], and to β-catenin via three 15-amino acid repeats and seven 20-amino acid repeats [29].
β-catenin (CTNNB1) Murine bcat.jpg

The N-terminus accommodates a critical sequence of thirteen armadillo repeats that competitively bind E-cadherin, LEF-1 and APC [30]. The C-terminus houses a glycine-rich transactivation domain [31]

Involved in mediating both morphogenesis and maintenance of tissue integrity in the endothelium, bound to a-catenin that subsequently binds to the actin cytoskeleton. Gene expression is mediated in conjunction with TCF/LEF, upon translocation from the cytosol into the nucleus [30]
  • The axin/APC/GSK-β complex phosphorylates b-catenin and marks it for ubiquitination and degradation by the proteasome [2]

The N-terminus constitutes the β-catenin interaction domain; TCF/LEF also possesses a HMG box DNA-binding domain [31]

Mediates DNA binding when in complex with β-catenin; the N-terminus of TCF/LEF associates with the β-catenin C-terminus [31]
  • CamKII, a serine/threonine-specific protein kinase product of the non-canonical Wnt/Ca2+ pathway, inhibits LEF-1 downstream of β-catenin, acting at the transcription factor complex level [19]

Dear everyone, don't forget to add caption text to your pictures. We need to write a little bit explaining what difference having the picture there makes, versus what is taken out of the picture if it's not there. So far no one has captioned their image so just pointing it out before it gets pointed out in peer review.

--Z3336051 21:51, 9 May 2012 (EST)

edit: On second thoughts, make that optional. Mark didn't write any text under his images on the lecture pages...

Hi Lee,

Actually I was doing the history :) -- Nat's taking care of the diseases associated with the signaling pathway. To be honest, the figure doesn't have too much to do with the history but it was the only relevant one I could find that could be posted on the website. I don't know if you noticed but all the references for the history come from big journals like Nature and Cell and so you have copyright issues.

I can try to relate the history to the figure or vice versa so things make more sense. Good job everyone!

Cheers, Sara --Z3333421 11:21, 7 May 2012 (EST)

Hi Nat (I think you're doing history now right?)

I noticed you posted up a figure of the β-catenin/XAxin-CBD complex. Since we're all madly posting content right now I understand why you haven't written up the explanation for the figure yet. I know no one else in our group has either (including me) but I ask about this one in particular because I'm a bit confused as to what it has to do with history.. I want to better understand what everyone else is doing, because it'll be more helpful than not for me to track what everyone else is doing, in putting together content for my section.

And to everyone else, especially Sara who has put in so much effort (and more than what she needed to!), sorry I haven't been contributing much so far. Been drowning in more work than I expected. This week however, cell bio will be my first priority subject in terms of workload. Partly because our page will be locked for peer evaluation by Thursday anyway.

Keep working hard everyone! Our page is slowly but surely taking form :) And please give me honest feedback as to anything you feel I should be doing but aren't doing currently. I would rather a group member point it out first so it can be fixed before someone else catches on during peer review assessment.

Cheers, Lee --Z3336051 21:19, 5 May 2012 (EST)

Thanks Sara for the table! It'll be a big help to decluttering my content.

--Z3336051 15:08, 4 May 2012 (EST)

Hey Sara, I can't work out how to create a table! If you have time, can you please one with these headings

- disease
- description
- causes
- symptoms
- treatment
- picture

Thanks :)

--Z3289738 15:26, 3 May 2012 (EST)

Hey guys, I've just edited some of the history, added a new pic (that wasn't copyrighted), updated the glossary and added content to embryonic development.

Lee, I also added a table that might be helpful in organising the content for the key players section.

--Z3333421 13:09, 3 May 2012 (EST)

Thanks Sara, I've started editing the disease section so all good now :)

I've just added/modified the subheadings for the page. Natalie, which section would you like to swap diseases with?

--Z3333421 21:35, 20 April 2012 (EST)

Hi guys, I've just uploaded the history which is not quite finished yet and I have to add in the references cheers.

--Z3333421 09:42, 19 April 2012 (EST)

Hey guys, Here's another simple diagram of the Wnt signaling cascade (on the right)

File:The Wnt Signaling cascade, simplified.png
Figure._Schematic_representation_of_a_colon_crypt_and_proposed_model_for_polyp_formation [2]

See you tomorrow

Just found a pretty good diagram showing the "on" and "off" states of the Wnt signalling pathway

Sam --Z3332227 17:21, 18 April 2012 (EST)

I've just written up a few notes on Wnt/Beta-catenin signalling. I haven't added the references in yet and i'm still looking for some good diagrams that explain it simply.

Sam --Z3332227 15:48, 10 April 2012 (EST)

Hey everyone, so to make it official, the task assigned to us for our project pages this week has officially been to upload one image each onto the wiki. I add one extra goal for our group to achieve by the end of this mid sem break; to begin writing relevant information under our assigned subheadings, and sourcing our information from four articles, by referencing it correctly.

Keep posting here, to keep each other updated on each of our progresses, and to keep the thoughts flowing.

Enjoy your breaks!

Lee --Z3336051 21:22, 6 April 2012 (EST)

Hey guys, I found four articles relating to abnormal function of the pathway:

Paper 1

Taketo, M Mark. "Shutting down Wnt signal-activated cancer." Nature Genetics 36. (2004): 320-22. DOI: 10.1038/ng0404-320 <pubmed>15054482</pubmed>

In this article, New evidence suggests that Wnt signaling can be suppressed or further activated by upstream signals, even though the pathway seems to be constitutively activated by downstream mutations in cancer cells.

Paper 2


This article highlights some key aspects of Wnt/β-catenin signaling in human diseases including congenital malformations, cancer, and osteoporosis, and discuss potential therapeutic implications

Paper 3


This review discusses some of the strategies that are being used or can be explored to target key components of the Wnt/β-catenin signaling pathway in rational cancer drug discover.

Paper 4


This review considers the spectra of tumors arising from active Wnt signaling and attempts to place perspective on recent data that begin to elucidate the mechanisms prompting uncontrolled cell growth following induction of Wnt signaling.

--Z3289738 10:48, 29 March 2012 (EST)

Check this out. It's a website all about the Wnt pathway. It has a list of virtually all review articles on the pathway.

<pubmed>9529612</pubmed> A review of the Wnt/beta-catenin pathway and the protein and receptor interactions involved.

<pubmed>9407023</pubmed> Outlines the evidence for the interaction of the Frizzled receptor with the Wnt protein.

<pubmed>15001769</pubmed> Explores the interrelationship between the Wnt, beta-catenin and cadherin pathways by examining the role of receptor activation and repression to control gene expression.

<pubmed>15652476</pubmed> Newer research made possible by advancements in imaging technology have better elucidated the finer interactions in the Wnt/beta-catenin pathway.

--Z3336051 23:36, 25 March 2012 (EST)

<pubmed>19619488</pubmed> Overview of the Wnt signaling pathway; ligands, agonists and antagonists and their interactions with Wnt receptors. Also mentions its implication in the development of human disease.

<pubmed>12775774</pubmed> Main extracellular antagonists of the Wnt signalling pathway - regulation of cell growth/differentiation.

<pubmed>19279722</pubmed> Involvement of Wnt signalling molecules in the control of embryonic development.

<pubmed>18392048</pubmed> Role of the Wnt pathway in proliferation, differentiation and apoptosis in adult tissues (and therefore oncogenesis).

--Z3332227 12:27, 25 March 2012 (EST)

Thank you so much Li! I'm happy with the are my references for this week's homework

<pubmed>16793760</pubmed> This review article provides a concise overview of the Wnt/Beta Catenin Signalling which can used in the introduction.

<pubmed>15372092</pubmed> There are a number of clearly labelled diagrams in this article that can be used as a starting point for the student drawn image.

<pubmed>18673238</pubmed> This article provides an historical overview of the key events that shaped our understanding of Wnt/Beta Catenin signalling and hence can greatly aid the history section.

<pubmed>17081971</pubmed> This review also contains many simplified diagrams that can be used to support the student drawn image.

--Z3333421 22:32, 22 March 2012 (EST)

Unfortunately we didn't get notch signalling, so we'll go with Wnt/beta-catenin signalling? To Natalie, the reason we didn't go with JAK/STAT was because of the apparent lack of research available on it. Wnt/beta-catenin seems better understood.

The following is a recommended assignment of sections, so we can get to our homework which is to each find four references for our respective assignment sections.

If you would like to swap, these roles are negotiable, but keep in mind that our homework is due next week.

  • Introduction + History + pathway images (at least one drawn) - Sara
  • Normal Function - Sam
  • Abnormal Function - Natalie
  • Receptors involved + (if applicable)Proteins involved - Li

To Sara, I wasn't quite sure how to divide up the subheadings based on the roles you wrote down, but you're free to reassign if you can elaborate for me. The above is my attempt at filling in the details.

Finally, I will look after maintenance of page formatting. Come to me if you have any questions.

--Z3336051 16:46, 22 March 2012 (EST)

Hey guys, If we decide to go with notch signaling here's a really great diagram & description:

--Z3289738 14:28, 22 March 2012 (EST)

  1. <pubmed>19619488</pubmed>
  2. 2.0 2.1 2.2 2.3 <pubmed>12781368</pubmed>
  3. Cite error: Invalid <ref> tag; no text was provided for refs named PMID9407023
  4. 4.0 4.1 4.2 Cite error: Invalid <ref> tag; no text was provided for refs named PMID11806834
  5. 5.0 5.1 5.2 5.3 Cite error: Invalid <ref> tag; no text was provided for refs named PMID9312064
  6. Cite error: Invalid <ref> tag; no text was provided for refs named PMID9118212
  7. Cite error: Invalid <ref> tag; no text was provided for refs named PMID10201374
  8. Cite error: Invalid <ref> tag; no text was provided for refs named PMID10067895
  9. 9.0 9.1 9.2 Cite error: Invalid <ref> tag; no text was provided for refs named PMID11357136
  10. Cite error: Invalid <ref> tag; no text was provided for refs named PMID9096311
  11. 11.0 11.1 Cite error: Invalid <ref> tag; no text was provided for refs named PMID9230313
  12. Cite error: Invalid <ref> tag; no text was provided for refs named PMID11029008
  13. Cite error: Invalid <ref> tag; no text was provided for refs named PMID11336703
  14. Cite error: Invalid <ref> tag; no text was provided for refs named PMID12050670
  15. Cite error: Invalid <ref> tag; no text was provided for refs named PMID7744250
  16. Cite error: Invalid <ref> tag; no text was provided for refs named PMID11752446
  17. Cite error: Invalid <ref> tag; no text was provided for refs named PMID12756182
  18. Cite error: Invalid <ref> tag; no text was provided for refs named PMID11970895
  19. 19.0 19.1 Cite error: Invalid <ref> tag; no text was provided for refs named PMID11472835
  20. 20.0 20.1 Cite error: Invalid <ref> tag; no text was provided for refs named PMID9482734
  21. Cite error: Invalid <ref> tag; no text was provided for refs named PMID10196136
  22. Cite error: Invalid <ref> tag; no text was provided for refs named PMID12027456
  23. 23.0 23.1 Cite error: Invalid <ref> tag; no text was provided for refs named PMID12000790
  24. Cite error: Invalid <ref> tag; no text was provided for refs named PMID8638126
  25. Cite error: Invalid <ref> tag; no text was provided for refs named PMID10428961
  26. Cite error: Invalid <ref> tag; no text was provided for refs named PMID8887544
  27. Cite error: Invalid <ref> tag; no text was provided for refs named PMID
  28. Cite error: Invalid <ref> tag; no text was provided for refs named PMID9554852
  29. Cite error: Invalid <ref> tag; no text was provided for refs named PMID10526234
  30. 30.0 30.1 Cite error: Invalid <ref> tag; no text was provided for refs named PMID10966653
  31. 31.0 31.1 31.2 Cite error: Invalid <ref> tag; no text was provided for refs named PMID9118222