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PDBsum entry 5i4z
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Transcription
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PDB id
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5i4z
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References listed in PDB file
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Key reference
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Title
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Omomyc blunts promoter invasion by oncogenic myc to inhibit gene expression characteristic of myc-Dependent tumors.
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Authors
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L.A.Jung,
A.Gebhardt,
W.Koelmel,
C.P.Ade,
S.Walz,
J.Kuper,
B.Von eyss,
S.Letschert,
C.Redel,
L.D'Artista,
A.Biankin,
L.Zender,
M.Sauer,
E.Wolf,
G.Evan,
C.Kisker,
M.Eilers.
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Ref.
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Oncogene, 2017,
36,
1911-1924.
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PubMed id
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Abstract
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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.
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