DOT1L stimulates MYC/Mondo transcription factor activity by promoting its degradation cycle on chromatin.
bioRxiv
; 2024 Feb 07.
Article
in En
| MEDLINE
| ID: mdl-38370658
ABSTRACT
The proto-oncogene c-MYC is a key representative of the MYC transcription factor network regulating growth and metabolism. MML-1 (Myc- and Mondo-like) is its homolog in C. elegans. The functional and molecular cooperation between c-MYC and H3 lysine 79 methyltransferase DOT1L was demonstrated in several human cancer types, and we have earlier discovered the connection between C. elegans MML-1 and DOT-1.1. Here, we demonstrate the critical role of DOT1L/DOT-1.1 in regulating c-MYC/MML-1 target genes genome-wide by ensuring the removal of "spent" transcription factors from chromatin by the nuclear proteasome. Moreover, we uncover a previously unrecognized proteolytic activity of DOT1L, which may facilitate c-MYC turnover. This new mechanism of c-MYC regulation by DOT1L may lead to the development of new approaches for cancer treatment.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
BioRxiv
Year:
2024
Document type:
Article
Affiliation country:
United States
Country of publication:
United States