Yeast cells with vacuoles marked with a fluorescent tag. Henderson et al. 2014 (CC-BY 4.0)
When a healthy cell creates new proteins, it activates a standard two-step biological manufacturing process. Firstly, DNA is transcribed from a specific gene to generate a strand of messenger RNA, or mRNA. Next, this mRNA molecule is translated to create the final protein product. This process of converting DNA into mRNA is supported by a series of helper proteins, including proteins from the bromodomain and extra-terminal domain (BET) family.
Cancer cells can become ‘addicted’ to the process of converting DNA into RNA, leading to the overproduction of mRNA molecules, uncontrolled cell growth and tumor formation. Knocking out BET helper proteins could potentially bring cancer cells under control by halting transcription and preventing tumor growth. However, the precise ways in which BET helper proteins regulate transcription are currently poorly understood, and therefore developing rational ways to target them is a challenge.
Building on their previous work, Donczew and Hahn have investigated how two BET helper proteins, Bdf1 and Bdf2, help to regulate transcription in budding yeast. Using a range of genomic techniques, Donczew and Hahn found that Bdf1 and Bdf2 had important roles for initiating transcription and elongating mRNA molecules. Both BET proteins were also involved in recruiting other protein factors to help with the transcription process, including TFIID and Mediator. Based on these findings, it is likely that cooperation between BET proteins, TFIID and Mediator represents a common pathway through which gene expression is regulated across all eukaryotic organisms.
Both Bdf1 and Bdf2 were also found to provide the same functions in yeast as similar BET proteins in humans. Using this robust yeast model system to perform further detailed studies of BET factors could therefore provide highly relevant information to expand our understanding of human biology and disease.
Ultimately, this research provides important insights into how two members of the BET family of helper proteins contribute to the control of transcription in yeast. This information could be used to guide the design of new drugs for cancer therapy that target not only BET proteins themselves but also other proteins they recruit, including TFIID and Mediator. Such targeted drugs would be expected to be more harmful for cancer cells than for healthy cells, which could reduce unwanted side effects.
