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Gaceta médica de México
versión On-line ISSN 2696-1288versión impresa ISSN 0016-3813
Resumen
MONTALVO-MENDEZ, Rubén J.; CARDENAS-TUEME, Marcela y RESENDEZ-PEREZ, Diana. Drosophila in the study of hTBP protein interactions in the development and modeling of SCA17. Gac. Méd. Méx [online]. 2024, vol.160, n.1, pp.1-9. Epub 26-Mar-2024. ISSN 2696-1288. https://doi.org/10.24875/gmm.23000214.
Background:
Protein interactions participate in many molecular mechanisms involved in cellular processes. The human TATA box binding protein (hTBP) interacts with Antennapedia (Antp) through its N-terminal region, specifically via its glutamine homopeptides. This PolyQ region acts as a binding site for other transcription factors under normal conditions, but when it expands, it generates spinocerebellar ataxia 17 (SCA17), whose protein aggregates in the brain prevent its correct functioning.
Objective:
To determine whether the hTBP glutamine-rich region is involved in its interaction with homeoproteins and the role it plays in the formation of protein aggregates in SCA17.
Material and methods:
We characterized hTBP interaction with other homeoproteins using BiFC, and modeled SCA17 in Drosophila melanogaster by targeting hTBPQ80 to the fly brain using UAS/GAL4.
Results:
There was hTBP interaction with homeoproteins through its glutamine-rich region, and hTBP protein aggregates with expanded glutamines were found to affect the locomotor capacity of flies.
Conclusions:
The study of hTBP interactions opens the possibility for the search for new therapeutic strategies in neurodegenerative pathologies such as SCA17.
Palabras llave : Homeoproteins; hTBP; Protein interactions; SCA17.