Back

MYC-induced oncogenesis is dependent on acidic patches within its N-terminal intrinsically disordered domain.

Llombart, V.; O'Connor, D.; Demeulemeester, J.; Bhamra, A.; Surinova, S.; Turna, A.; Fung, K.; Wang, L.; Li, Y.; Rapoz-D'Silva, T.; Ahmed, F.; Niskanen, H.; Stöppelkamp, I.; Hnisz, D.; Bottaro, S.; Fisicaro, C.; He, S.; Look, A. T.; Mansour, M. R.

2025-06-19 cancer biology
10.1101/2025.06.16.659507 bioRxiv
Show abstract

MYC is one of the most enticing therapeutic targets for cancer but clinical-grade inhibitors are still lacking. By site-saturation mutagenesis screening, we identified several evolutionarily conserved acidic patches within the intrinsically-disordered MYC N-terminus that were confirmed to be functionally essential in different cell models and in vivo. Beyond modulating MYCs global transcriptional activity, these negatively charged patches regulate the interaction with chromatin-modifying complexes including those with histone acetyl-transferase activity. One of the key interactions is established with the co-factor TRRAP, a subunit shared between several Histone Acetyl-Transferase complexes. The protein-protein binding between MYC and TRRAP predominantly relies on two of the N-terminal negative clusters that are located outside MYC-Box-II (MBII) and drive oncogenesis. Our work identifies a new multivalent MYC subdomain that presents new therapeutic vulnerabilities providing invaluable insights for the development of new therapeutic approaches.

Matching journals

The top 5 journals account for 50% of the predicted probability mass.

1
Nucleic Acids Research
◐ 1281 papers in training set
Top 1%
14.6%
Similar papers in this journal
2
eLife
● 5828 papers in training set
Top 9%
10.8%
Similar papers in this journal
3
Nature Communications
○ 5641 papers in training set
Top 19%
9.5%
Similar papers in this journal
4
Science Advances
● 1243 papers in training set
Top 1%
9.5%
Similar papers in this journal
5
Oncogene
○ 85 papers in training set
Top 0.3%
6.1%
Similar papers in this journal
50% of probability mass above
6
EMBO Reports
○ 263 papers in training set
Top 1%
4.0%
7
Life Science Alliance
● 285 papers in training set
Top 1%
3.2%
8
Molecular & Cellular Proteomics
183 papers in training set
Top 0.7%
3.1%
9
The EMBO Journal
○ 309 papers in training set
Top 2%
2.3%
10
Journal of Biological Chemistry
○ 690 papers in training set
Top 4%
2.3%
11
Proceedings of the National Academy of Sciences
● 2444 papers in training set
Top 25%
2.0%
12
Molecular Cancer Research
● 49 papers in training set
Top 0.7%
1.7%
13
NAR Cancer
◐ 37 papers in training set
Top 0.3%
1.7%
14
Science Signaling
● 65 papers in training set
Top 0.6%
1.7%
15
Cell Reports
○ 1498 papers in training set
Top 21%
1.5%
16
Biochemical Journal
● 91 papers in training set
Top 0.9%
1.4%
17
PLOS ONE
● 5266 papers in training set
Top 54%
1.1%
18
iScience
○ 1154 papers in training set
Top 28%
1.1%
19
Communications Biology
○ 993 papers in training set
Top 23%
1.1%
20
Molecular Systems Biology
○ 162 papers in training set
Top 3%
1.0%
21
Cancer Research
● 130 papers in training set
Top 3%
0.8%
22
PLOS Genetics
● 862 papers in training set
Top 12%
0.8%
23
Redox Biology
○ 70 papers in training set
Top 2%
0.8%
24
Frontiers in Immunology
○ 638 papers in training set
Top 11%
0.6%
25
Scientific Reports
○ 3612 papers in training set
Top 78%
0.6%
26
Cellular and Molecular Life Sciences
○ 96 papers in training set
Top 3%
0.6%

"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.