ABSTRACT
All human cells throughout an individual’s body contain roughly the same genome, that is, the DNA molecules which represent the blueprints of biology inherited from one’s parents. ese blueprints contain the information necessary to create tens of thousands of dierent proteins, which are the molecular machines that are fundamental to all of cellular biology, performing a wide range actions such as metabolizing nutrients, allowing a cell to respond to its environment, and even controlling the quantities, or “expression levels,” of other proteins. One particularly important protein, p53, is oen referred to as “the guardian of the genome” and is implicated in many biological processes and diseases including cancer. As an individual grows and ages, cells
must repeatedly make copies of their own genomes, which eventually results in degradation of the information contained therein. When enough errors accumulate, it is possible for a cell to enter a broken, cancerous state in which it grows continuously, damaging nearby tissue and causing harm to the organism. e p53 protein is a major player in the cell’s natural defense against entering such a state: p53 responds to the detection of genomic problems by increasing the expression of hundreds of other proteins to try to x the errors, or, if that isn’t possible, it can even cause a cell to destroy itself, saving the neighboring cells and the life of the individual. One way that p53 is able to react to such problems is due to signals from a set of proteins that chemically modify p53 in response to dierent conditions. Each p53 modication, of which there are over 50, acts as an on/o switch, causing p53 to have one response or another. e most common type of modication among all proteins, including p53 in particular, is phosphorylation, in which a phosphate molecule (PO43−) is bonded to a specic atom in a protein molecule. e class of proteins that carries out the addition of phosphate molecules are known as kinases, which are increasingly the target of promising cancer treatments for use when these signaling mechanisms. Drugs can aect the behavior of specic kinases, which can produce specic reactions in the proteins they phosphorylate, with the goal being to activate the cell’s innate cancer-ghting abilities. Knowing which proteins are kinases is a well-solved problem; however, knowing which proteins are modied by each kinase, and therefore which kinases would make good drug targets, is a dicult and unsolved problem. ere are over 500 known human kinases and tens of thousands of possible proteins they can target. Biochemical experiments require months to establish a single novel kinaseprotein relationship, and then years to fully elucidate the relationship’s biological impact. Only 33 of the 500+ kinases are currently known to modify p53, but it is likely that there are many such relationships that remain unknown.
