27/06/2014

UIC Research Team Discovers How Nutrients Regulate Cell Proliferation

A UIC research team led by Dr. Josep Clotet has discovered how nutrients regulate cell proliferation, thus providing an answer to one of the great questions raised in biology books. The team published its results in the high-impact American journal Molecular and Cellular Biology (MCB). At the same time, a research team from the University of Illinois at Chicago (UIC) independently came to the same conclusion. Both universities review their results in the journal Cell Cycle. The results are one more step forward in the fight against cancer.

Cell proliferation is governed by proteins called cyclin-dependent kinases (CDK). The name comes from their total dependence on other proteins called cyclins, which are in charge of forming an active enzyme complex that allows the cell cycle to progress. In mammals, when nutrient levels are high enough to start a new life cycle, the amount of cyclin D is increased and the CDK4/cyclin D complexes formed allow for a new cell cycle to initialize.

In the American journal Molecular and Cellular Biology, Dr. Clotet's team published studies that describe how the cyclin D from the yeast Saccharomyces cerevisiae (Cln3) is stabilized in response to the presence of available phosphate in the medium. In yeast, the presence of phosphate activates the PHO pathway, whose nucleus is the protein Pho85. The results of the studies show that, when phosphate is present, Pho85 regulates Cln3 levels by increasing the stability of cyclin, thereby promoting cell cycle progression.

Inversely, in the absence of phosphate in the medium, Cln3 is degraded and, therefore, much more unstable, leading to a cell cycle arrest. The relevance of this finding is proven in mutants whose Pho85 pathway is always active. These cells maintain stable Cln3 levels and grow at an abnormal and uncontrollable rate, even in the absence of nutrients in the medium.

UIC Versus UIC

This same discovery was made simultaneously and independently by Dr. Stephen Kron's research team at the University of Illinois at Chicago (UIC) and was published in the prestigious journal Cell Cycle. Dr. Kron also postulates that chaperones may play a key role in stabilizing cyclin D and clearly shows that the mechanism is present in human cells.

Most cancerous tumours present an abnormal amount of cyclin D. In fact, high levels of cyclin D are usually an indicator of a poor prognosis in the evolution of the disease.

Both Dr. Clotet's and Dr. Kron's teams analyse these results and their possible applications in a joint article published in the journal Cell Cycle. There is no doubt that the results will help improve knowledge about what mechanisms tumour cells use to have such runaway growth and are one more step in the long road in the fight against cancer.