The finger loop of the SRA domain in the E3 ligase UHRF1 is a regulator of ubiquitin targeting and is required for the maintenance of DNA methylation.
DNA methylation
DNA-binding protein
E3 ubiquitin ligase
SRA domain
allosteric regulation
epigenetics
molecular dynamics
string method in collective variables
ubiquitin-like with PHD and RING finger domains 1 (UHRF1)
Journal
The Journal of biological chemistry
ISSN: 1083-351X
Titre abrégé: J Biol Chem
Pays: United States
ID NLM: 2985121R
Informations de publication
Date de publication:
25 10 2019
25 10 2019
Historique:
received:
11
07
2019
revised:
29
08
2019
pubmed:
5
9
2019
medline:
3
6
2020
entrez:
5
9
2019
Statut:
ppublish
Résumé
The Su(var)3-9, enhancer of zeste, and trithorax (SET) and really interesting new gene (RING) finger-associated (SRA) protein domain is conserved across bacteria and eukaryota and coordinates extrahelical or "flipped" DNA bases. A functional SRA domain is required for ubiquitin-like with PHD and RING finger domains 1 (UHRF1) E3 ubiquitin ligase activity toward histone H3, a mechanism for recruiting the DNA methylation maintenance enzyme DNA methyltransferase 1 (DNMT1). The SRA domain supports UHRF1 oncogenic activity in colon cancer cells, highlighting that UHRF1 SRA antagonism could be a cancer therapeutic strategy. Here we used molecular dynamics simulations, DNA binding assays,
Identifiants
pubmed: 31481468
pii: S0021-9258(20)30334-3
doi: 10.1074/jbc.RA119.010160
pmc: PMC6816099
doi:
Substances chimiques
CCAAT-Enhancer-Binding Proteins
0
Phosphates
0
Ubiquitin
0
DNA
9007-49-2
UHRF1 protein, human
EC 2.3.2.27
Ubiquitin-Protein Ligases
EC 2.3.2.27
Banques de données
PDB
['2ZKD', '3CLZ', '3Q0C', '4NJ5', '4QEN', '4PW6']
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
15724-15732Subventions
Organisme : NCI NIH HHS
ID : F99 CA245821
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM124736
Pays : United States
Informations de copyright
© 2019 Vaughan et al.
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