5I4Z

Structure of apo OmoMYC

5I4Z の概要

• エントリーDOI: 10.2210/pdb5i4z/pdb
• 分子名称: Myc proto-oncogene protein, GLYCEROL, CHLORIDE ION, ... (5 entities in total)
• 機能のキーワード: leucine zipper, transcription factor, tumor suppressor, e-box, transcription
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Nucleus, nucleoplasm : P01106
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 28532.93

構造登録者

Koelmel, W.,Jung, L.A.,Kuper, J.,Eilers, M.,Kisker, C. (登録日: 2016-02-13, 公開日: 2016-10-26, 最終更新日: 2024-11-20)

主引用文献

Jung, L.A.,Gebhardt, A.,Koelmel, W.,Ade, C.P.,Walz, S.,Kuper, J.,von Eyss, B.,Letschert, S.,Redel, C.,d'Artista, L.,Biankin, A.,Zender, L.,Sauer, M.,Wolf, E.,Evan, G.,Kisker, C.,Eilers, M.
OmoMYC blunts promoter invasion by oncogenic MYC to inhibit gene expression characteristic of MYC-dependent tumors.
Oncogene, 36:1911-1924, 2017

PubMed 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.

PubMed: 27748763
DOI: 10.1038/onc.2016.354

実験手法

X-RAY DIFFRACTION (1.95 Å)