Human MDM2 peptide

Loss of retinoblastoma (RB) function in the cone cells during retina development is necessary but not sufficient for retinoblastoma development. It has been reported that in the absence of RB activity, a retinoma is generated, and the onset of retina cancer occurs until the p53 pathway is altered. Unlike other types of cancer, in retinoblastoma the p53 tumour suppressor is mostly wild type, although its two primary regulators, MDMX and MDM2, are commonly dysregulated. A mutated RB form is inherited in around 35% of the cases, but normally two, somatic mutations are needed to alter the RB function. Here we investigated the mRNA levels of RB, p53, MDMX and MDM2 in peripheral blood samples of retinoblastoma patients to monitor the pathway status of p53 in somatic cells. We sought to investigate the involvement of these genes in the development of retina cancer, with the aim of identifying biomarkers for early diagnosis of this disease.

Via regulation of cellular stress responses, p53 contributes to the maintenance of homeostasis. Contrary to its well-established pro-death function, p53 is also implicated in promoting cell survival by mediating the adaptive stress response. Emerging data reveal that the adaptive stress response is coupled with p53 decline that is a prerequisite for the induction of pro-survival pathways augmenting cell fitness. However, if the adaptive stress responses persist or become chronic, the sustained p53 downregulation would result in a permanent loss of p53 function and p53-dependent homeostasis. The available information suggests a model in which cells respond to different levels of stress by governing the activity and abundance of p53 that, in turn, determines the cell fate dependent on not only the intensity but also the duration of stress.