TY  - JOUR
A1  - Diebold, Mathias
A1  - Schönemann, Lars
A1  - Eilers, Martin
A1  - Sotriffer, Christoph
A1  - Schindelin, Hermann
T1  - Crystal structure of a covalently linked Aurora-A-MYCN complex
T2  - Acta Crystallographica
N2  - Formation of the Aurora-A–MYCN complex increases levels of the oncogenic transcription factor MYCN in neuroblastoma cells by abrogating its degradation through the ubiquitin proteasome system. While some small-molecule inhibitors of Aurora-A were shown to destabilize MYCN, clinical trials have not been satisfactory to date. MYCN itself is considered to be `undruggable' due to its large intrinsically disordered regions. Targeting the Aurora-A–MYCN complex rather than Aurora-A or MYCN alone will open new possibilities for drug development and screening campaigns. To overcome the challenges that a ternary system composed of Aurora-A, MYCN and a small molecule entails, a covalently cross-linked construct of the Aurora-A–MYCN complex was designed, expressed and characterized, thus enabling screening and design campaigns to identify selective binders.
KW  - MYCNv
KW  - neuroblastoma cell
KW  - proteasome system
Y1  - 2023
UR  - https://opus.bibliothek.uni-wuerzburg.de/opus4-wuerzburg/frontdoor/index/index/docId/31885
UR  - https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-318855
VL  - D79
SP  - 1
EP  - 9
ER  -