Identification of therapeutic and diagnostic targets through yeast two hybrid system: molecular biology in medicine

Abstract

In the last decades, molecular biology development was driven medicine, mainly in identification of novel therapeutic and diagnostics targets. In cells, proteins are the main responsible for the functioning of all cellular processes, from DNA synthesis to RNA and protein production, transport of cellular components and structural composition of the cell. Proteins are also an important component of signaling pathways between cells. Studies show that proteins normally do not function as singular units but as protein complexes. Understand protein interactions and discover compounds that interfere with such protein complexes are important to develop new pharmacologic treatments. There are already some drugs with such characteristics. Trichostatin A, a histone diacetilase, acts in Phosphatase protein 1 - Histone diacetilase complex, being a good target for anti-cancer therapy. In 1989, in a revolutionary way, Fields and Songs developed the Yeast Two Hybrid system (YTH). This method is based in the genetic properties of Saccharomyces cerevisiae and allows the detection of protein interactions in vivo. Since its development it suffered a few modifications that allowed its application in translational medicine. For example, this technique allows a high throughput screening to assess if a drug can interfere with a protein interaction. In the other hand, YTH can be used to ascertain which proteins interact with a protein of interest in a specific tissue (for example, brain or testis). Thus it is possible to unveil protein functions, signaling pathways and tissue functions. The great amount of data produced with YTH allows the identification and validation of diagnostic and therapeutic targets and also the development of new drugs. This review has the purpose to clarify the YTH system function and its contribution in identification of new pharmacologic treatments.