In silico analysis of ubiquitin and its target protein interaction in yeast and human

Abstract

Cellular protein levels are carefully maintained to regulate the expression and functional activity of proteins. Cells have their own mechanism to synthesize the proteins and switch on its function temporally. Likewise, there are also mechanisms to suppress the activity of proteins when they are no longer needed. The aforementioned variability in the dynamics of protein expression in cell is tightly controlled by maintaining a perfect balance between the rate of synthesis and degradation of proteins. Ubiquitinmediated proteasome and lysosomal proteolysis are two main pathways through which proteins are degraded in eukaryotic cells. Ubiquitin Proteasome System (UPS) is known to be a salvage pathway for protein degradation since deregulation of UPS pathway is responsible for onset of many diseases including cancer, diabetes, and neurodegenerative diseases. Most of the intracellular proteins targeted for degradation by UPS pathways are subjected to a post translational modification known as ubiquitination and enters into a 26S proteasomal complex where proteolysis takes place. Thus, ubiquitination marks the target for degradation in which a small protein, ubiquitin conjugates with a specific lysine residue (ubi-K) in the target protein. Once the bond is made, the attached ubiquitin can use a lysine residue to link another ubiquitin, producing a poly-ubiquitin chain. The type of ubiquitination, the location of conjugated lysine in ubiquitin and subcellular localization of substrate give rise to a multitude of functions including proteasomal degradation, non-proteolytic events like DNA repair, transcription, induction of inflammatory response, antigen presentation. Deregulation of ubiquitination may cause decreased levels of tumor suppressor proteins or increased level of oncoproteins that are known toinduce abnormal cell proliferation and cancer development. Therefore, understanding the mechanism of ubiquitination, especially the ubiquitin binding environment of target proteins is essential in development of appropri