STRUCTURAL VARIATION IN E3 LIGASES UBIQUITINATION PLATFORM

摘要

p53 is a tumor suppressor protein, called also "The Guardian of the cells and genome" and one of the most effective defensive weapons of human body against carcinogenesis. Activation and/or inactivation of p53 is a critical step in the tumor suppression/formation process, respectively. The suppression of p53 levels is being indirectly regulated by the protein itself, which activates the expression of the oncogene mdm2 (murine double minute 2), which expresses the HDM2 protein. HDMX, a HDM2 homologue, is also being implicated in p53 suppression. The C-terminal regions of HDM2 and HDMX are RING finger domains and catalyze the last stage of protein signaling for proteolysis, through the ubiquitin pathway acting therefore as E3 ubiquitin ligases. The activity of p53 as a transcription factor is strongly coupled to HDM2 protein overexpression which is a molecular mechanism of the cell towards p53 ubiquitinylation, degradation and inactivation.