Baker's yeast (Saccharomyces cerevisiae) is a single celled eukaryotic fungus that is commonly used as a model organism. There are many reasons that yeast is a favorite eukaryote to study: yeast are easy to grow, nonpathogenic, easy to transform with DNA, easy to mate, stable as both a haploid and a diploid and recombination happens frequently. Additionally, yeast has been highly studied yielding a lot of background (over 53,000 scientific papers in the last 40 years) and the DNA sequence of the entire genome has been available since 1996. From this sequence, we know that yeast has just 6,145 genes (compared to 30,000 - 150,000 genes in humans). Despite the large number of papers published on my favorite organism, only just over half of the genes have been studied so far, leaving plenty of work to be done. For more information on yeast as a model eukaryote, see Fred Sherman's excellent review article, An Introduction to the Genetics and Molecular Biology of the Yeast Saccharomyces cerevisiae.
The RAS Signal Transduction Pathway and Yak1
Ras is one of the most commonly mutated genes in human cancers. It is estimated that up to one third of all cancer contain mutations that activate the Ras gene and that this activated Ras gene contributes to the formation of the cancer. Ras acts as a molecular switch; when Ras is 'on' it tells the cell to grow and divide. S. cerevisiae also has a Ras gene that functions similarly to the human gene (indeed, if one replaces the yeast gene with the human gene, the human gene works just fine in yeast). Therefore, we can learn more about how the Ras protein functions in people by studying the Ras protein in yeast.
How does the Ras protein transmit the "grow" signal into the cell? It relays the information through a series of proteins and small molecules in an arrangement referred to as a signal transduction pathway. The Yak1 protein is a part of this pathway. Yak1 is a protein kinase, which means that it enzymatically attaches phosphates to other proteins and that these modifications will change the functions of the target proteins. However, Yak1 activity opposes the Ras signal. Therefore, activated Yak1p sends a "don't grow" signal and the loss of Yak1p enhances growth. Precisely how Yak1 inhibits growth remains unknown but is a topic of great interest.
MSI1 suppresses the RAS Signal Transduction
Msi1p is another yeast protein that can also suppress the RAS pathway in yeast. More than 15 years ago, it was discovered that extra copies of could turn off this pathway but the mechanism by which MSI1 works has remained elusive to this day. Strangely, Msi1p seems to do other things in the cell too, including wrapping newly synthesized DNA around structural proteins and turing RNA synthesis on and off. Because it is such a surprise, it makes an interesting project to pursue. We have previously discovered that Msi1p appears to affect the RAS pathway by blocking the function of the Npr1p kinase.
Both Yak1p and Msi1p (through Npr1p) deactivate the RAS pathway by unknown mechanisms. Could these two proteins both be using the same means to affect RAS? That might well be the case and could help us understand both of them. In our recent Journal of Molecular Biology paper, we show that Msi1p and Yak1p cooperate on several activites. For example, extra copies of Yak1p slow cell growth, but only if Msi1p is present in the cell. Similarly, the presence of Yak1p promotes the accumulation of Msi1p in the nucleus when the cell is consuming sub-optimal food sources.
So how do these three genes connect to RAS? That is the current focus of the Yeast Lab. We are in the process of identifying yeast genes that either cooperate or inhibit the ability of Yak1p/Msi1p to slow growth as we expect this to lead us to the direct connection to the RAS pathway.
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Pictures of the People in the Yeast Lab
Last updated: March 26, 2007
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