close
test_template

How Mdm2 and P53 Associate in Normal Physiology Ho

download print

About this sample

About this sample

close

Words: 720 |

Pages: 2|

4 min read

Published: Dec 5, 2018

Words: 720|Pages: 2|4 min read

Published: Dec 5, 2018

The paper I chose for this assignment was “Regulation of the Mdm2-p53 pathway by the ubiquitin E3 ligase MARCH7” (Zhao et al., 2017). I determined that I wanted to use this paper as it directly relates to the specific lecture topics we’ve gone over already.

'Why Violent Video Games Shouldn't Be Banned'?

A slide in the lecture from Tuesday, 1/16, introduced the p53 tumor suppressor gene. A schematic showed that in the absence of damaged DNA, p53 is not activated via ATP and instead binds to Mdm2 for degradation. The paper I chose directly related to the mechanism which occurs between p53 and Mdm2 and its implications for cancer research. Mdm2 is an ubiquitin E3 ligase and it ubiquitinates p53, which targets it for degradation via the proteasome (Zhao et al., 2017).

The purpose of this paper was to elucidate the regulatory mechanisms for Mdm2 itself, which are less understood. Mdm2 is required to control the levels of p53 in cells; in unstressed, healthy cells, Mdm2 allows for the degradation of p53 as it is not needed (Zhao et al., 2017). It was determined that another ubiquitin E3 ligase, MARCH7, was responsible for the regulation of Mdm2 itself (Zhao et al., 2017).

This paper suggested a novel mechanism in which p53 is regulated through Mdm2, and by extension, MARCH7. Furthermore, it is suggested that Mdm2 might be involved with a regulatory loop based on whether it is ubiquitinated or de-ubiquitinated (Zhao et al., 2017). The experiments performed for this paper illuminated the role that MARCH7 plays with Mdm2 and p53. MARCH7 binds to and stabilizes Mdm2 through polyubiquitination, therefore, it promotes the degradation of p53 (Zhao et al., 2017). The individual experiments sought to determine the effect of the presence or lack thereof of ubiquitination MARCH7 on p53. An interesting discrepancy the researchers found between previous findings and their own was between the autoubiquitination and polyubiquitination of Mdm2 (Zhao et al., 2017).

Previous findings suggest that Mdm2 is regulated through autoubiquitination, however, new findings suggest that other types of ubiquitination are responsible for this regulation (Zhao et al., 2017). The new findings from this paper suggest that the full extent of MARCH7 activity in the polyubiquitination of Mdm2 may be obscured by autoubiquitination (Zhao et al., 2017). This autoubiquitination would utilize a different amino acid binding site as opposed to MARCH7, which acts on K48 or K63 (Zhao et al., 2017). Ubiquitination at K48 or K63 act as completely separate signals.

Polyubiquitination at K48 acts as a signal for degradation at the proteasome whereas at K63, ubiquitin is regulatory and does not act as a pro-proteasomal signal (Zhao et al., 2017). This difference is essential to the conclusion of the researchers that Mdm2 and MARCH7 are possibly involved in a regulatory loop determined by whether Mdm2 is ubiquitinated or de-ubiquitinated (Zhao et al., 2017). If p53 is indeed controlled directly by Mdm2, then the presence of a regulatory loop involving the ubiquitination state of Mdm2 could be an extremely valuable target for medical intervention. This regulatory loop involves the ubiquitination or de-ubiquitination of Mdm2. The study effectively showed that MARCH7 ubiquitinates and stabilizes Mdm2, however, Mdm2 is also stabilized by a de-ubiquitinating entity called HAUSP (Zhao et al., 2017).

The loops are formed since MARCH7 also can interact with HAUSP, where HAUSP regulates the concentration of MARCH7 (Zhao et al., 2017). While the effects of HAUSP and MARCH7 on Mdm2 are more defined, the relationship between HAUSP and MARCH7 directly require further investigation. The researchers postulate that should these relationships act as described in their research, this could very well lead to the development of methodologies to reactivate p53 by disabling the ability of Mdm2 to associate with p53 to be degraded (Zhao et al., 2017).

Get a custom paper now from our expert writers.

Overall I thought this was an extremely interesting paper which allowed for a greater understanding of the context from class. The paper seemed to effectively elucidate how Mdm2 and p53 associate in normal physiology as well as cancer. I especially found it interesting that not only did the researchers describe how the ubiquitin E3 ligase MARCH7 regulates the interaction between Mdm2 and p53, but they also provided a possible regulatory loop. The understanding that p53 is not simply degraded or not by Mdm2 through different pathways, but could be controlled by a common variable, HAUSP, further upstream is extremely interesting.

Image of Alex Wood
This essay was reviewed by
Alex Wood

Cite this Essay

How Mdm2 and p53 associate in normal physiology Ho. (2018, December 03). GradesFixer. Retrieved March 28, 2024, from https://gradesfixer.com/free-essay-examples/how-mdm2-and-p53-associate-in-normal-physiology-ho/
“How Mdm2 and p53 associate in normal physiology Ho.” GradesFixer, 03 Dec. 2018, gradesfixer.com/free-essay-examples/how-mdm2-and-p53-associate-in-normal-physiology-ho/
How Mdm2 and p53 associate in normal physiology Ho. [online]. Available at: <https://gradesfixer.com/free-essay-examples/how-mdm2-and-p53-associate-in-normal-physiology-ho/> [Accessed 28 Mar. 2024].
How Mdm2 and p53 associate in normal physiology Ho [Internet]. GradesFixer. 2018 Dec 03 [cited 2024 Mar 28]. Available from: https://gradesfixer.com/free-essay-examples/how-mdm2-and-p53-associate-in-normal-physiology-ho/
copy
Keep in mind: This sample was shared by another student.
  • 450+ experts on 30 subjects ready to help
  • Custom essay delivered in as few as 3 hours
Write my essay

Still can’t find what you need?

Browse our vast selection of original essay samples, each expertly formatted and styled

close

Where do you want us to send this sample?

    By clicking “Continue”, you agree to our terms of service and privacy policy.

    close

    Be careful. This essay is not unique

    This essay was donated by a student and is likely to have been used and submitted before

    Download this Sample

    Free samples may contain mistakes and not unique parts

    close

    Sorry, we could not paraphrase this essay. Our professional writers can rewrite it and get you a unique paper.

    close

    Thanks!

    Please check your inbox.

    We can write you a custom essay that will follow your exact instructions and meet the deadlines. Let's fix your grades together!

    clock-banner-side

    Get Your
    Personalized Essay in 3 Hours or Less!

    exit-popup-close
    We can help you get a better grade and deliver your task on time!
    • Instructions Followed To The Letter
    • Deadlines Met At Every Stage
    • Unique And Plagiarism Free
    Order your paper now