Grant: Travel Awards - Institute Community Support

In our research group, we study cell senescence, which is a state of proliferative arrest. Cell senescence occurs after DNA damage, such as that induced by anti-cancer therapy. p21 and p53 are two major regulators of cell senescence. P53 acts by inducing the production of various factors, including p21. P21 is a protein responsible for halting proliferation. We are interested in studying cell senescence in Ovarian Cancer. There are different subtypes of ovarian cancer. Most of them are p53 deficient, but they are all p21 proficient but some of them are p53 and p21 proficient. Our previous study shows that ovarian cancer deficient in p53 can enter senescence. Moreover, we have shown that these senescent cells are susceptible to specific drugs for senescent cells called senolytics. Thus, our objective is to understand how p21 is regulated independently of p53 during senescence in ovarian cancer. We discovered that p21 behaves differently at two different times after DNA damage: it becomes active early on and then again later when cells enter senescence. To investigate this, we discovered p21SEN, a part of the p21 gene that is only activated during senescence and not in the early phase. This allowed us to monitor p21's activity in real time during senescence. We also used computer analyses to identify molecules that control p21SEN's activity and then tested these in the lab. Our findings confirmed that p21SEN becomes active during senescence, even when another important protein called p53 is not present. We also discovered that a molecule called NF-kB promotes p21SEN activity, while another molecule called SP1 represses it. We believe that our discovery has important implications for understanding senescence and could be used in future studies to develop tools for ovarian cancer therapy.