Sandbox Reserved 1227

From Proteopedia

(Difference between revisions)

Revision as of 15:03, 25 April 2017

This Sandbox is Reserved from Jan 17 through June 31, 2017 for use in the course Biochemistry II taught by Jason Telford at the Maryville University, St. Louis, USA. This reservation includes Sandbox Reserved 1225 through Sandbox Reserved 1244.

To get started:

Click the edit this page tab at the top. Save the page after each step, then edit it again.
Click the 3D button (when editing, above the wikitext box) to insert Jmol.
show the Scene authoring tools, create a molecular scene, and save it. Copy the green link into the page.
Add a description of your scene. Use the buttons above the wikitext box for bold, italics, links, headlines, etc.

More help: Help:Editing

MDM2

Function

Mdm2 is an E3 ubiquitin ligase that ubiquitylates and targets p53 for degradation. MDM2 and the closely related MDM4 are two of the main inhibitory proteins of the p53 pathway. The p53 pathway is activated when the cell is distressed and needs to be broken down. The p53 pathway leads to the ceasing of proliferation of the cell, or cell death. Too much MDM2 can turn off the p53 pathway, allowing the cell to grow uncontrollably, allowing for tumor growth. The association between p53 and the MDM proteins can be seen in . On the other hand, if MDM2 or MDM4 is under regulated, p53 will overwork, causing cell death more often and earlier on than necessary.^[1]

Relevance

Often, the p53 pathway is compromised due to the over expression of proteins such as MDM2 or MDM4. This over expression can lead to decreased activity of p53 which allows the cell to proliferate even when the body signals it to be destroyed. This is thought to be one of the lead causes of tumor progression^[1]. Data involving MDM2 and the SNP285 polymorphism within its promotor region have been researched, and this region has been shown to be significantly linked to a decreased cancer risk^[2]. It is believed that further MDM2 research and therapy could possibly lead to an anticancer strategy ^[3].

Structural highlights

Although there is a lot of research currently underway that involves the MDM2-p53 interactions, it is unsure exactly how these two molecules interact. This is in part because MDM2’s receptor structure contains highly flexible parts. There is evidence that has shown that as the binding with p53 occurs, the MDM2 structure changes conformation from “closed” to “open.” In the closed conformation, there is an N-terminus fragment (residues 25-109) that forms a lid that covers its hydrophobic binding site. This shows that there are many intermediate levels of binding for the MDM2 complex. During the interaction with p53, it is thought that the N-terminus fragment interacts with a short, helical region of p53 ^[4].

References

↑ Eischen, C. M., & Lozano, G. (2014). The Mdm network and its regulation of p53 activities: a rheostat of cancer risk. Human Mutation, 35(6), 728–737. http://doi.org/10.1002/humu.22524
↑ Wang, P., Wang, M., Li, S., Ma, L., Xi, S., & He, J. (2016). Association of the MDM2 SNP285 Polymorphism with Cancer Susceptibility: A Meta-Analysis. Disease Markers, 20164585484.
↑ Trino, S., De Luca, L., Laurenzana, I., Caivano, A., Del Vecchio, L., Martinelli, G., & Musto, P. (2016). P53-MDM2 Pathway: Evidences for A New Targeted Therapeutic Approach in B-Acute Lymphoblastic Leukemia. Frontiers in Pharmacology, 7, 491. http://doi.org/10.3389/fphar.2016.00491.
↑ Ciemny, M. P., Debinski, A., Paczkowska, M., Kolinski, A., Kurcinski, M., & Kmiecik, S. (2016). Protein-peptide molecular docking with large-scale conformational changes: the p53-MDM2 interaction. Scientific Reports, 6, 37532. http://doi.org/10.1038/srep37532.

Retrieved from "http://52.214.119.220/wiki/index.php/Sandbox_Reserved_1227"

@@ Line 10: / Line 10: @@
 == Structural highlights ==
-Although there is a lot of research currently underway that involves the MDM2-p53 interactions, it is unsure exactly how these two molecules interact. This is because part of MDM2’s receptor structure contains highly flexible parts. There is evidence that has shown that as the binding with p53 occurs, the MDM2 structure changes conformation from “closed” to “open.” In the closed conformation, there is an N-terminus fragment (residues 25-109) that forms a lid that covers its hydrophobic binding site. This shows that there are many intermediate levels of binding for the MDM2 complex. During the interaction with p53, it is thought that the N-terminus fragment interacts with a short, helical region of p53 <ref>Ciemny, M. P., Debinski, A., Paczkowska, M., Kolinski, A., Kurcinski, M., & Kmiecik, S. (2016). Protein-peptide molecular docking with large-scale conformational changes: the p53-MDM2 interaction. Scientific Reports, 6, 37532. http://doi.org/10.1038/srep37532.</ref>.
+Although there is a lot of research currently underway that involves the MDM2-p53 interactions, it is unsure exactly how these two molecules interact. This is in part because MDM2’s receptor structure contains highly flexible parts. There is evidence that has shown that as the binding with p53 occurs, the MDM2 structure changes conformation from “closed” to “open.” In the closed conformation, there is an N-terminus fragment (residues 25-109) that forms a lid that covers its hydrophobic binding site. This shows that there are many intermediate levels of binding for the MDM2 complex. During the interaction with p53, it is thought that the N-terminus fragment interacts with a short, helical region of p53 <ref>Ciemny, M. P., Debinski, A., Paczkowska, M., Kolinski, A., Kurcinski, M., & Kmiecik, S. (2016). Protein-peptide molecular docking with large-scale conformational changes: the p53-MDM2 interaction. Scientific Reports, 6, 37532. http://doi.org/10.1038/srep37532.</ref>.
 </StructureSection>
 == References ==
 {{Reflist}} <references/>

Sandbox Reserved 1227

From Proteopedia

Revision as of 15:03, 25 April 2017

MDM2

Function

Relevance

Structural highlights

References

Views

Personal tools

Navigation

Search

Toolbox