Ubiquitylation in Cancer Regulation
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My internship focused on the pro-pathogenic role of ubiquitylation in cancer. Ubiquitylation is a post-translational modification that controls many highly regulated, biological processes that are vital to maintaining cell homeostasis (Duan & Pagano et al., 2021). Dysregulation of the ubiquitin system has been associated with the initiation and development of cancer (Mansour., 2018). Depending on the target protein, ubiquitin may function as a tumor suppressor or tumor promoter by inhibiting or activating a number of different cascades (Hoeller & Dikic., 2009). In my internship, I was directly involved in helping Grant with his practicum that focused on the endogenous role of DCAF15, an ubiquitin E3 ligase, in the development of 5Acute Myeloid Leukemia (AML). An Acute Myeloid Leukemia dataset from the Cancer Genome Atlas (TCGA) revealed that patients with high DCAF15 expression had poorer survival rates compared to their counterparts with low DCAF15 expression (TCGA). Nonetheless, the mechanism behind which DCAF15 is able to facilitate this reaction and its substrate is largely unknown. To determine potential DCAF15 substrates in the Cohesin complex, Amelia, who was a previous research intern and Grant, ran a CRISPR/CAS9 screen of proteins that underwent MLN treatment and saw several proteins binded to DCAF15. The protein, CDCA5 also known as Sororin, in particular, stood out because of its role in regulating the Cohesin complex. Hence, I was personally responsible for conducting a CDCA5 Truncation-Mapping IP and CDCA5 Mutagenesis Mapping IP with the intention of determining the region of Sororin that DCAF15 binds to.