Myc 9aaTAD activation domain binds to mediator of transcription with superior high affinity
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F65269705%3A_____%2F24%3A00080558" target="_blank" >RIV/65269705:_____/24:00080558 - isvavai.cz</a>
Alternative codes found
RIV/00216224:14110/24:00137688
Result on the web
<a href="https://molmed.biomedcentral.com/articles/10.1186/s10020-024-00896-7" target="_blank" >https://molmed.biomedcentral.com/articles/10.1186/s10020-024-00896-7</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1186/s10020-024-00896-7" target="_blank" >10.1186/s10020-024-00896-7</a>
Alternative languages
Result language
angličtina
Original language name
Myc 9aaTAD activation domain binds to mediator of transcription with superior high affinity
Original language description
The overexpression of MYC genes is frequently found in many human cancers, including adult and pediatric malignant brain tumors. Targeting MYC genes continues to be challenging due to their undruggable nature. Using our prediction algorithm, the nine-amino-acid activation domain (9aaTAD) has been identified in all four Yamanaka factors, including c-Myc. The predicted activation function was experimentally demonstrated for all these short peptides in transactivation assay. We generated a set of c-Myc constructs (1-108, 69-108 and 98-108) in the N-terminal regions and tested their ability to initiate transcription in one hybrid assay. The presence and absence of 9aaTAD (region 100-108) in the constructs strongly correlated with their activation functions (5-, 3- and 67-times respectively). Surprisingly, we observed co-activation function of the myc region 69-103, called here acetyl-TAD, previously described by Faiola et al. (Mol Cell Biol 25:10220-10234, 2005) and characterized in this study as a new domain collaborating with the 9aaTAD. We discovered strong interactions on a nanomolar scale between the Myc-9aaTAD activation domains and the KIX domain of CBP coactivator. We showed conservation of the 9aaTADs in the MYC family. In summary for the c-Myc oncogene, the acetyl-TAD and the 9aaTAD domains jointly mediated activation function. The c-Myc protein is largely intrinsically disordered and therefore difficult to target with small-molecule inhibitors. For the c-Myc driven tumors, the strong c-Myc interaction with the KIX domain represents a promising druggable target.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30100 - Basic medicine
Result continuities
Project
<a href="/en/project/NV19-05-00410" target="_blank" >NV19-05-00410: Role of cytotoxic gamma-delta T cells implicated in therapeutic resistence and tumour recurrence in Glioblastoma Multiforme</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2024
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Molecular Medicine
ISSN
1076-1551
e-ISSN
1528-3658
Volume of the periodical
30
Issue of the periodical within the volume
1
Country of publishing house
US - UNITED STATES
Number of pages
9
Pages from-to
211
UT code for WoS article
001354434200004
EID of the result in the Scopus database
2-s2.0-85209214494