Phosphorylation of the Mdm2 oncoprotein by the c-Abl tyrosine kinase regulates p53 tumor suppression and the radiosensitivity of mice
Year: 2016
Type: article
Abstract: Significance The p53 transcription factor is stabilized in response to cellular stress and regulates the expression of genes involved in numerous biological activities, thereby suppressing tumorigenesis. DNA damage and other stress signals upregulate p53, in part, by freeing p53 from negative regulation imposed by the Mdm2 and MdmX (Mdm4) oncoproteins. MDM proteins are subject to posttranslational modification, and accumulating evidence indicates that phosphorylation of Mdm2 by different stress-activated kinases such as ATM or c-Abl alters Mdm2-p53 signaling and profoundly affects p53 function. A better understanding of the in vivo effects of Mdm2 phosphorylation may facilitate the development of novel therapeutics capable of stimulating p53 antitumor activity or alleviating p53-dependent toxicities in nonmalignant tissues.
Institution: University of Massachusetts Chan Medical School
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2561900603