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 to use this article as it directly relates to the specific lesson topics we have already covered. Say no to plagiarism. Get a tailor-made essay on "Why Violent Video Games Shouldn't Be Banned"? Get an original essay One slide in the lecture on Tuesday, January 16 introduced the tumor suppressor gene p53. One scheme showed that in the absence of damaged DNA, p53 is not activated via ATP and instead binds to Mdm2 for degradation. 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 E3 ubiquitin ligase and p53 ubiquitin, targeting 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 non-stressed cells, Mdm2 allows the degradation of p53 as it is not required (Zhao et al., 2017). It was determined that another ubiquitin E3 ligase, MARCH7, was responsible for regulating Mdm2 itself (Zhao et al., 2017). This article suggested a novel mechanism in which p53 is regulated through Mdm2 and, by extension, MARCH7. Furthermore, it is suggested that Mdm2 might be involved in a regulatory loop based on whether it is ubiquitinated or de-ubiquitinated (Zhao et al., 2017). The experiments performed for this article illuminated the role that MARCH7 plays with Mdm2 and p53. MARCH7 binds and stabilizes Mdm2 through polyubiquitination, thus promotes p53 degradation (Zhao et al., 2017). Individual experiments sought to determine the effect of the presence or lack of MARCH7 ubiquitination on p53. One interesting discrepancy the researchers found between previous results and theirs concerned 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 of this article suggest that the full extent of MARCH7 activity in Mdm2 polyubiquitination may be obscured by autoubiquitination (Zhao et al., 2017). This autoubiquitination would utilize 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 signal for proteasomal degradation while at K63 ubiquitin is regulatory and does not act as a pro-proteasomal signal (Zhao et al., 2017). This difference is essential for researchers to conclude that Mdm2 and MARCH7 are likely involved in a regulatory loop determined by whether Mdm2 is ubiquitinated or de-ubiquitinated (Zhao et al., 2017). If p53 is indeed directly controlled 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 cycle involves the ubiquitination or de-ubiquitination of Mdm2. The study indeed demonstrated that MARCH7 ubiquitinates and stabilizes Mdm2, however, Mdm2 is also stabilized by a deubiquitinating entity called HAUSP (Zhao et al., 2017). The loops are formed because MARCH7 can also interact with HAUSP, where HAUSP regulates the concentration of MARCH7 (Zhao et al., 2017). While the effects of HAUSP and MARCH7 on Mdm2 are.