DNMT3A Stability Is Maintained by Ubiquitin-Specific Peptidase 11 (USP11) and Sumoylation Countering Degradation
Yonezawa, T.; Rutter, J.; Ramabadran, R.; Sundaramurthy, V.; Datar, G.; Slabicki, M.; Goodell, M. A.
Show abstract
DNA methyltransferase 3A (DNMT3A) plays crucial roles in mammalian development and hematopoiesis. DNMT3A protein instability is associated with blood diseases such as myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), as well as Tatton-Brown-Rahman syndrome, an overgrowth disorder. We found that certain unstable DNMT3A mutations cause DNMT3A localization changes, resulting in loss of function. This mislocalization is partially rescued by E1 enzyme inhibition or stable USP11 expression, as DNMT3A stability is maintained by deubiquitinating enzyme USP11 countering degradation by CUL4-DCAF8 E3 ligase. We also found that USP11 enhances DNMT3A SUMOylation by promoting the interaction between DNMT3A and SUMO E3 ligases. DNMT3A SUMOylation also is essential to maintain DNMT3A protein stability. Furthermore, we found USP11 enhances the binding of DNMT3A to the polycomb complex and maintains DNMT3A DNA methyltransferase (MTase) activity. This study uncovers the mechanism for DNMT3A protein turnover through USP11, which is essential to DNMT3A function, and may be a therapeutic approach for diseases caused by DNMT3A protein instability.
Matching journals
The top 15 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Metabolic reprogramming of cancer cells by JMJD6-mediated pre-mRNA splicing is associated with therapeutic response to splicing inhibitor 94%
- Super-Enhancer Driven ZFP36L1 Promotes PD-L1 Expression in Infiltrative Gastric Cancer 94%
- UBTD1 regulates ceramide balance and endolysosomal positioning to coordinate EGFRsignaling 94%
Similar papers in this journal
- NRF1 and NRF3 complementarily maintain a basal proteasome activity in cancer cells through CPEB3-mediated translational repression 93%
- Histone chaperone Nucleophosmin regulates transcription of key genes involved in oral tumorigenesis. 93%
- Contribution of CENP-F to FOXM1-mediated discordant centromere and kinetochore transcriptional regulation 93%
Similar papers in this journal
- High-throughput single-cell DNA methylation and chromatin accessibility co-profiling with SpliCOOL-seq 92%
- Loss-of-Function genetic Screen Unveils Synergistic Efficacy of PARG Inhibition with Combined 5-Fluorouracil and Irinotecan Treatment in Colorectal Cancer 91%
- Epigenetic Consequences of Hormonal Interactions between Opposite-sex Twin Fetuses 91%
Similar papers in this journal
- Epitranscriptomic editing of the RNA N6-methyladenosine modification by dCasRx conjugated methyltransferase and demethylase 94%
- Loss of Lamin A leads to the nuclear translocation of AGO2 and compromised RNA interference 94%
- Site-specific acetylation of polynucleotide kinase 3-phosphatase (PNKP) regulates its distinct role in DNA repair pathways 94%
Similar papers in this journal
- USP7 as part of non-canonical PRC1.1 is a druggable target in leukemia 95%
- The E3 ubiquitin ligase DTX3L and the deubiquitinase USP28 fine-tune DNA double strand repair through mutual regulation of their protein levels 94%
- A Non-genetic Mechanism for Chemoresistance in Lung Cancer: The Role of Integrin β4/Paxillin Axis 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.