OmoMYC blunts promoter invasion by oncogenic MYC to inhibit gene expression characteristic of MYC-dependent tumors.
View / Open Files
Authors
Jung, LA
Gebhardt, A
Koelmel, W
Ade, CP
Walz, S
Kuper, J
von Eyss, B
Letschert, S
Redel, C
d'Artista, L
Biankin, A
Zender, L
Sauer, M
Wolf, E
Kisker, C
Publication Date
2017-04-06Journal Title
Oncogene
ISSN
0950-9232
Volume
36
Issue
14
Language
English
Type
Article
This Version
AM
Metadata
Show full item recordCitation
Jung, L., Gebhardt, A., Koelmel, W., Ade, C., Walz, S., Kuper, J., von Eyss, B., et al. (2017). OmoMYC blunts promoter invasion by oncogenic MYC to inhibit gene expression characteristic of MYC-dependent tumors.. Oncogene, 36 (14)https://doi.org/10.1038/onc.2016.354
Abstract
MYC genes have both essential roles during normal development and exert oncogenic functions during tumorigenesis. Expression of a dominant-negative allele of MYC, termed OmoMYC, can induce rapid tumor regression in mouse models with little toxicity for normal tissues. How OmoMYC discriminates between physiological and oncogenic functions of MYC is unclear. We have solved the crystal structure of OmoMYC and show that it forms a stable homodimer and as such recognizes DNA in the same manner as the MYC/MAX heterodimer. OmoMYC attenuates both MYC-dependent activation and repression by competing with MYC/MAX for binding to chromatin, effectively lowering MYC/MAX occupancy at its cognate binding sites. OmoMYC causes the largest decreases in promoter occupancy and changes in expression on genes that are invaded by oncogenic MYC levels. A signature of OmoMYC-regulated genes defines subgroups with high MYC levels in multiple tumor entities and identifies novel targets for the eradication of MYC-driven tumors.
Sponsorship
Cancer Research UK (19013)
Cancer Research UK (22585)
Identifiers
External DOI: https://doi.org/10.1038/onc.2016.354
This record's URL: https://www.repository.cam.ac.uk/handle/1810/295282
Rights
Licence:
http://www.rioxx.net/licenses/all-rights-reserved