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Title: Protein methylation, a new mechanism of p53 tumor suppressor regulation
Issue Date: 2008
Publisher: Murcia : F. Hernández
ISSN: 0213-3911
Related subjects: 616 - Patología. Medicina clínica. Oncología
Keywords: Methylation
Abstract: The tumor suppressor p53 is the most frequently inactivated gene in human cancers. The p53 protein functions as a sequence-specific transcription factor to regulate key cellular processes, including cellcycle arrest, DNA repair, apoptosis, and senescence in response to stress signals. P53 is maintained at a low level in the cell, but becomes rapidly stabilized and activated in response to DNA damage, hypoxia, hyperproliferation, and other types of cellular stresses. The stability and transcriptional activity of p53 are tightly regulated through multiple post-translational modifications, such as phosphorylation, acetylation, and ubiquitination. Within the past few years, several studies have established that protein methylation is a novel mechanism by which p53 is regulated. Indeed, histone lysine methyltransferases KMT5 (Set9), KMT3C (Smyd2), and KMT5A (Set8) methylate p53 at specific C-terminal lysines. Lysine methylation enhances or suppresses p53 transcriptional activity depending on the methylation site. Furthermore, the lysine-specific demethylase KDM1 (LSD1) mediates p53 demethylation, which prevents p53 interaction with its co-activator 53BP1 to induce apoptosis. Finally, protein arginine methyltransferases CARM1 and PRMT1 are coactivators of p53 involved in the methylation of histones H3 and H4 to facilitate p53-mediated transcription. In response to cellular stresses, the interplay between p53 methylation, demethylation, and other post-translational modifications fine-tunes the activity of p53 to ultimately prevent tumor formation.
Primary author: Scoumanne, A.
Chen, X.
Published in: Histology and histopathology
Document type: info:eu-repo/semantics/article
Number of pages / Extensions: 7
Rights: info:eu-repo/semantics/openAccess
Appears in Collections:Vol.23, nº9 (2008)

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