SIRT1 regulates the localization and stability of telomerase protein by direct interaction.
Biochem Biophys Res Commun
; 720: 150098, 2024 08 06.
Article
en En
| MEDLINE
| ID: mdl-38749190
ABSTRACT
Telomerase reverse transcriptase (TERT) not only upholds telomeric equilibrium but also plays a pivotal role in multiple non-canonical cellular mechanisms, particularly in the context of aging, cancer, and genomic stability. Though depletion of SIRT1 in mouse embryonic fibroblasts has demonstrated telomere shortening, the impact of SIRT1 on enabling TERT to regulate telomeric homeostasis remains enigmatic. Here, we reveal that SIRT1 directly interacts with TERT, and promotes the nuclear localization and stability of TERT. Reverse transcriptase (RT) domain of TERT and N-terminus of SIRT1 mainly participated in their direct interaction. TERT, concomitantly expressed with intact SIRT1, exhibits nuclear localization, whereas TERT co-expressed with N-terminal-deleted SIRT1 remains in the cytosol. Furthermore, overexpression of SIRT1 enhances the nuclear localization and protein stability of TERT, akin to overexpression of deacetylase-inactive SIRT1, whereas N-terminal-deleted SIRT1 has no effect on TERT. These findings suggest a novel regulatory role of SIRT1 for TERT through direct interaction. This interaction provides new insights into the fields of aging, cancer, and genome stability governed by TERT and SIRT1.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Telomerasa
/
Sirtuina 1
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Biochem Biophys Res Commun
Año:
2024
Tipo del documento:
Article
Pais de publicación:
Estados Unidos