Protein methylation

A new mechanism of p53 tumor suppressor regulation

A. Scoumanne, Xinbin Chen

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

Summary. 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 cell-cycle 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 co-activators 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.

Original languageEnglish (US)
Pages (from-to)1143-1149
Number of pages7
JournalHistology and Histopathology
Volume23
Issue number9
StatePublished - Sep 2008

Fingerprint

Methylation
Lysine
Post Translational Protein Processing
Neoplasms
Proteins
Histones
Histone-Lysine N-Methyltransferase
Protein-Arginine N-Methyltransferases
Apoptosis
Ubiquitination
Acetylation
Cell Cycle Checkpoints
DNA Repair
DNA Damage
Transcription Factors
Phosphorylation
Genes

Keywords

  • Cancer
  • Methylation
  • Methyltransferases
  • P53
  • Transcription

ASJC Scopus subject areas

  • Histology
  • Pathology and Forensic Medicine

Cite this

Protein methylation : A new mechanism of p53 tumor suppressor regulation. / Scoumanne, A.; Chen, Xinbin.

In: Histology and Histopathology, Vol. 23, No. 9, 09.2008, p. 1143-1149.

Research output: Contribution to journalArticle

@article{b2f491a89d1543edae38c2aeeff6b1e7,
title = "Protein methylation: A new mechanism of p53 tumor suppressor regulation",
abstract = "Summary. 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 cell-cycle 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 co-activators 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.",
keywords = "Cancer, Methylation, Methyltransferases, P53, Transcription",
author = "A. Scoumanne and Xinbin Chen",
year = "2008",
month = "9",
language = "English (US)",
volume = "23",
pages = "1143--1149",
journal = "Histology and Histopathology",
issn = "0213-3911",
publisher = "Histology and Histopathology",
number = "9",

}

TY - JOUR

T1 - Protein methylation

T2 - A new mechanism of p53 tumor suppressor regulation

AU - Scoumanne, A.

AU - Chen, Xinbin

PY - 2008/9

Y1 - 2008/9

N2 - Summary. 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 cell-cycle 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 co-activators 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.

AB - Summary. 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 cell-cycle 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 co-activators 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.

KW - Cancer

KW - Methylation

KW - Methyltransferases

KW - P53

KW - Transcription

UR - http://www.scopus.com/inward/record.url?scp=84863986224&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84863986224&partnerID=8YFLogxK

M3 - Article

VL - 23

SP - 1143

EP - 1149

JO - Histology and Histopathology

JF - Histology and Histopathology

SN - 0213-3911

IS - 9

ER -