The article I chose for this assignment was “Regulation of the Mdm2-p53 pathway by the ubiquitin E3 ligase MARCH7” (Zhao et al., 2017). I decided I wanted to use this article because it directly relates to the specific course topics we have already covered. Say no to plagiarism. Get a tailor-made essay on “Why Violent Video Games Should Not Be Banned”? Get the original essay A slide from the lecture on Tuesday, January 16, featured the p53 tumor suppressor gene. A scheme showed that in the absence of damaged DNA, p53 is not activated via ATP but binds to Mdm2 to be degraded. The article I chose was directly related to the mechanism that 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 aim of this article was to elucidate the regulatory mechanisms of Mdm2 itself, which are less understood. Mdm2 is required to control p53 levels in cells; in healthy, unstressed cells, Mdm2 allows p53 degradation because it is not required (Zhao et al., 2017). Another ubiquitin E3 ligase, MARCH7, was determined to be responsible for the regulation of Mdm2 itself (Zhao et al., 2017). This article suggests a novel mechanism in which p53 is regulated via Mdm2 and, by extension, MARCH7. Furthermore, it is suggested that Mdm2 could be involved in a regulatory loop depending on whether it is ubiquitinated or deubiquitinated (Zhao et al., 2017). The experiments performed for this article shed light on the role that MARCH7 plays with Mdm2 and p53. MARCH7 binds to Mdm2 and stabilizes it by polyubiquitination; it therefore promotes the degradation of p53 (Zhao et al., 2017). Individual experiments aimed to determine the effect of the presence or absence of MARCH7 ubiquitination on p53. An interesting discrepancy found by the researchers between previous findings and their own concerns the autoubiquitination and polyubiquitination of Mdm2 (Zhao et al., 2017). Previous findings suggest that Mdm2 is regulated by autoubiquitination. However, new findings suggest that other types of ubiquitination are possible. responsible for this regulation (Zhao et al., 2017). The new results in this paper suggest that the full extent of MARCH7 activity in Mdm2 polyubiquitination may be obscured by autoubiquitination (Zhao et al., 2017). This autoubiquitination would use a different amino acid binding site than MARCH7, which acts on K48 or K63 (Zhao et al., 2017). Ubiquitination at K48 or K63 acts as completely separate signals. Polyubiquitination at K48 acts as a degradation signal at the proteasome while at K63, ubiquitin is regulatory and does not act as a pro-proteasomal signal (Zhao et al., 2017). This difference is essential to the researchers' conclusion that Mdm2 and MARCH7 are perhaps involved in a regulatory loop determined by whether Mdm2 is ubiquitinated or deubiquitinated (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 provide an extremely valuable target for medical intervention. This regulatory loop involves the ubiquitination or deubiquitination of Mdm2. The study indeed showed that MARCH7 ubiquitinates and stabilizes Mdm2, however, Mdm2 is also stabilized by a deubiquitinating entity called HAUSP (Zhao et al., 2017). The loops form since MARCH7 can also interact with HAUSP, where HAUSP regulates the concentration of MARCH7 (Zhao et al., 2017). Although the effects of HAUSP and MARCH7 on Mdm2 are.