Mutant p53 and its Isoforms in the Onset & Treatment of Breast Cancer BY BROOKLYN SCHROEDER ’22 Cover Image: P53 is a tetramer tumor suppressor protein. The above depicts the crystal structure of the p53 binding domains which are attached to the respective DNA binding site. Image Source: Wikimedia Commons
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Introduction The molecular mysteries of tumor onset and progression and their role in the development of a variety of cancers still perplex the modern world of science. Breast cancer, the most frequently diagnosed cancer in women in the United States, is no exception to this enigma. The manner in which a breast tumor develops is unique to a case-by-case basis. With this being said, regulation of cellular pathways, and especially their tumor suppressing properties, are critical in preventing this onset. The p53 protein, a tumor suppressor protein, is an essential transcription factor encoded by the TP53 gene and is essential in the regulation of a variety of cellular processes associated with apoptosis (a form of programmed cell death), cellular proliferation, cellular senescence (the ceasing of cell division), and also plays a critical role in DNA replication and repair activity. Most notably, in consideration of the development of cancerous tumors, especially in light of breast cancer, mutations in the p53 protein are characteristic of a considerable
fraction of breast cancer cases (Ziyaie et al., 2000). The p53 protein is a vitally important point of molecular focus in recognizing the onset of tumor development and can therefore be a biological marker for breast cancer treatments.
p53 Structure & Function The molecular structure of the p53 protein gives it characteristic function in the regulation of cell cycle arrest, DNA repair, and apoptotic pathways. By dissecting the structure of the p53 protein and its various domains, one can further recognize the extent to which this protein becomes nonfunctional by structural mutation. The p53 protein contains 393 amino acids, which are divided into various domains: the functional domain, which consists of a specific region called the transactivation region, a sequence-specific DNA binding region, oligomerization region, and a nuclear localization sequence (Harris, 1996). The other two key domains are categorized as evolutionary conserved domains deemed to be hotspots of mutational events (Harris, 1996). DARTMOUTH UNDERGRADUATE JOURNAL OF SCIENCE
