St Vincent's Institute

We could not survive or, for that matter, develop in the first place, if our cells were not capable of multiplying and dividing. Cells division occurs in an orderly and highly regimented way, following a defined sequence of events. Simply put, cells grow in size, duplicate their contents, and then divide in two. This process of duplication and division is called the cell cycle. When it goes awry, normal cell growth and behavior is disrupted and cancer develops.

The cell cycle is a major focus of interest for Boris Sarcevic, head of SVI’s Cell Cycle and Cancer Unit. Understanding how this complicated and highly regulated process is controlled, and how it can go wrong gives us a good chance of finding new ways to treat cancer.

Boris’ team focuses on two fundamental biological processes that control cell division: phosphorylation and ubiquitination.

Boris explains, ‘A major focus for my group is a family of proteins called the cyclin-dependent kinases (CDKs), which control cell division. These proteins work as a kind of engine; by activating important proteins, they drive the cell through its cycle of cell growth and division.’

He goes on to explain that CDKs are often overactive in cancer and responsible for the abnormal and increased growth of cancer cells. Although the pivotal role that CDKs play in the cell cycle is well accepted, the identity of the proteins and the growth pathways that they activate is not well understood.

Using novel methods developed at the Institute, researchers in the group have identified numerous proteins that are activated by CDKs. These studies may allow the development of drugs to stop the uncontrolled cellular proliferation that occurs in cancer.

The researchers are also interested in another important family of proteins: the ubiquitin-conjugating (E2s) and ubiquitin ligase (E3s) enzymes. These enzymes influence all biological pathways, but are of particular importance in the cell cycle, as they acts as an ‘accelerator’ of the cell cycle. If the process malfunctions, it can lead to uncontrolled proliferation, genomic instability and cancer.

Finding a ‘cure’ for cancer is so complicated because cancer cells cleverly find different ways of turning off cellular brakes and jamming on cellular accelerators. By understanding the engines that drive the cell cycle and the brakes that control it, researchers at SVI are moving a step closer to understanding the molecular mechanisms of cell division, providing important insights into human cancer and, most importantly, developing new cancer treatments.