The effect of p14ARF and YY1 peptides in MDM2-p53 mediated oncogenic pathway: An in silico perspective

摘要

It is a learned fact known over the years which implicates that controlled cell multiplication is required for mammalian homeostasis. However, uncontrolled multiplication is the sign of a tumor. In the view of developing group of literature, it is well understood that apoptosis is an essential routine during the event of oncogenesis in which Alternate reading frame (p14ARF) associates with Mouse double minute 2 (MDM2) causing enhancement in tumor suppression function of p53 by preventing its degradation. However, no molecular models were available to investigate the interacting subunits, interfaces and conformations. So there is a need to elucidate the structural framework containing p14ARF, MDM2 and p53 structural units. Using computer simulations, we observe a significant conformation change in one of the proteins termed p14ARF upon recognizing binding proteins. This triggers the process of attracting Ying Yang-1 (YY1) to the ternary complex to form a quaternary unit (p14ARF-MDM2-p53-YY1). This proposed model gives new insight on p53 mediated oncogenic pathway and can be used as a therapeutic target for identifying novel leads in cancer. Moreover, the present study also highlights the conformation of the peptide YY1, a turning point in MDM2-p53 oncogenic events.