Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Spreitzer, E; Alderson, TR; Bourgeois, B; Eggenreich, L; Habacher, H; Brahmersdorfer, G; Pritišanac, I; Sánchez-Murcia, PA; Madl, T.
FOXO transcription factors differ in their dynamics and intra/intermolecular interactions.
Curr Res Struct Biol. 2022; 4:118-133
Doi: 10.1016/j.crstbi.2022.04.001
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- Leading authors Med Uni Graz
- Madl Tobias
- Spreitzer Emil
- Co-authors Med Uni Graz
- Alderson Thomas Reid
- Bourgeois Benjamin Michel Rene
- Eggenreich Loretta
- Habacher Hermann Hans
- Pritisanac Iva
- Sánchez Murcia Pedro Alejandro
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- Abstract:
- Transcription factors play key roles in orchestrating a plethora of cellular mechanisms and controlling cellular homeostasis. Transcription factors share distinct DNA binding domains, which allows to group them into protein families. Among them, the Forkhead box O (FOXO) family contains transcription factors crucial for cellular homeostasis, longevity and response to stress. The dysregulation of FOXO signaling is linked to drug resistance in cancer therapy or cellular senescence, however, selective drugs targeting FOXOs are limited, thus knowledge about structure and dynamics of FOXO proteins is essential. Here, we provide an extensive study of structure and dynamics of all FOXO family members. We identify residues accounting for different dynamic and structural features. Furthermore, we show that the auto-inhibition of FOXO proteins by their C-terminal trans-activation domain is conserved throughout the family and that these interactions are not only possible intra-, but also inter-molecularly. This indicates a model in which FOXO transcription factors would modulate their activities by interacting mutually.
- Find related publications in this database (Keywords)
- Transcription factors
- Transcription activation domain
- NMR spectroscopy
- Protein dynamics
- Spin relaxation
- Molecular dynamics