Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.1.1.37 (
DNA methyltransferase
)
4,983
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Many non-histone proteins are lysine methylated and a novel function of this modification is to trigger the proteolysis of methylated proteins. Here, we report that the methylated lysine 142 of DNMT1, a major
DNA methyltransferase
that preserves epigenetic inheritance of DNA methylation patterns during DNA replication, is demethylated by LSD1. A novel methyl-binding protein, L3MBTL3, binds the K142-methylated DNMT1 and recruits a novel CRL4
DCAF5
ubiquitin ligase to degrade DNMT1. Both LSD1 and
PHF20L1
act primarily in S phase to prevent DNMT1 degradation by L3MBTL3-CRL4
DCAF5
. Mouse L3MBTL3/MBT-1 deletion causes accumulation of DNMT1 protein, increased genomic DNA methylation, and late embryonic lethality. DNMT1 contains a consensus methylation motif shared by many non-histone proteins including E2F1, a key transcription factor for S phase. We show that the methylation-dependent E2F1 degradation is also controlled by L3MBTL3-CRL4
DCAF5
. Our studies elucidate for the first time a novel mechanism by which the stability of many methylated non-histone proteins are regulated.
...
PMID:Methylated DNMT1 and E2F1 are targeted for proteolysis by L3MBTL3 and CRL4
DCAF5
ubiquitin ligase. 2969 1
