Epigenetics and beyond: targeting writers of protein lysine methylation to treat disease.
Animals
Antineoplastic Agents
/ pharmacology
Drug Development
/ methods
Epigenesis, Genetic
Histone Methyltransferases
/ antagonists & inhibitors
Histone-Lysine N-Methyltransferase
/ antagonists & inhibitors
Histones
/ metabolism
Humans
Lysine
/ metabolism
Methylation
Protein Processing, Post-Translational
Journal
Nature reviews. Drug discovery
ISSN: 1474-1784
Titre abrégé: Nat Rev Drug Discov
Pays: England
ID NLM: 101124171
Informations de publication
Date de publication:
04 2021
04 2021
Historique:
accepted:
09
11
2020
pubmed:
21
1
2021
medline:
23
6
2021
entrez:
20
1
2021
Statut:
ppublish
Résumé
Protein lysine methylation is a crucial post-translational modification that regulates the functions of both histone and non-histone proteins. Deregulation of the enzymes or 'writers' of protein lysine methylation, lysine methyltransferases (KMTs), is implicated in the cause of many diseases, including cancer, mental health disorders and developmental disorders. Over the past decade, significant advances have been made in developing drugs to target KMTs that are involved in histone methylation and epigenetic regulation. The first of these inhibitors, tazemetostat, was recently approved for the treatment of epithelioid sarcoma and follicular lymphoma, and several more are in clinical and preclinical evaluation. Beyond chromatin, the many KMTs that regulate protein synthesis and other fundamental biological processes are emerging as promising new targets for drug development to treat diverse diseases.
Identifiants
pubmed: 33469207
doi: 10.1038/s41573-020-00108-x
pii: 10.1038/s41573-020-00108-x
pmc: PMC8035164
mid: NIHMS1668650
doi:
Substances chimiques
Antineoplastic Agents
0
Histones
0
Histone Methyltransferases
EC 2.1.1.-
Histone-Lysine N-Methyltransferase
EC 2.1.1.43
Lysine
K3Z4F929H6
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
265-286Subventions
Organisme : NCI NIH HHS
ID : R01 CA218600
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM122749
Pays : United States
Organisme : NCI NIH HHS
ID : K00 CA212435
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA236118
Pays : United States
Organisme : NICHD NIH HHS
ID : R01 HD088626
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA230854
Pays : United States
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