Methylated Proteins are Targeted for Proteolysis by L3MBTL3 and CRL4-DCAF5 Ubiquitin E3 ligase
Document Type
Article
Publication Date
4-24-2018
Publication Title
Molecular Cell
Abstract
Lysine methylation is a major protein modification and emerging evidence indicates that many non-histone proteins are methylated to regulate their activity or protein stability. How the methylated non-histone proteins are recognized and processed remains largely unclear. Here we show that the methylated lysine residue that triggers the proteolysis of DNMT1, a major DNA methyltransferase that preserves epigenetic inheritance of DNA methylation patterns during DNA replication, is recognized by the Malignant Brain Tumor (MBT) domain of L3MBTL3 in a cell cycle-dependent manner. L3MBTL3 further interacts with the CRL4-DCAF5 ubiquitin ligase to target DNMT1 for proteolysis. Since the consensus methylation motif in DNMT1 is present in many non-histone proteins including E2F1, a key transcription factor for S-phase, we show that the methylation-dependent degradation of E2F1 is also controlled by the CRL4-DCAF5-L3MBTL3 complexes. Our studies thus reveal a novel and common mechanism by which the stability of many methylated non-histone proteins are regulated.
Language
eng
Repository Citation
Leng, F.,
Yu, J.,
Zhang, C.,
Alejo, S.,
Hoang, N.,
Sun, H.,
Lu, F.,
Zhang, H.
(2018).
Methylated Proteins are Targeted for Proteolysis by L3MBTL3 and CRL4-DCAF5 Ubiquitin E3 ligase.
Molecular Cell
http://dx.doi.org/10.1038/s41467-018-04019-9