VHL suppresses UBE3B-mediated breast tumor growth and metastasis.
Cell Death Dis
; 15(6): 446, 2024 Jun 24.
Article
en En
| MEDLINE
| ID: mdl-38914543
ABSTRACT
Protein homeostasis is predominantly governed through post-translational modification (PTM). UBE3B, identified as an oncoprotein, exhibits elevated protein levels in breast cancer. However, the impact of PTM on UBE3B remains unexplored. In this study, we show that VHL is a bona fide E3 ligase for UBE3B. Mechanistically, VHL directly binds to UBE3B, facilitating its lysine 48 (K48)-linked polyubiquitination at K286 and K427 in a prolyl hydroxylase (PHD)-independent manner. Consequently, this promotes the proteasomal degradation of UBE3B. The K286/427R mutation of UBE3B dramatically abolishes the inhibitory effect of VHL on breast tumor growth and lung metastasis. Additionally, the protein levels of UBE3B and VHL exhibit a negative correlation in breast cancer tissues. These findings delineate an important layer of UBE3B regulation by VHL.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Neoplasias de la Mama
/
Ubiquitina-Proteína Ligasas
/
Proteína Supresora de Tumores del Síndrome de Von Hippel-Lindau
/
Ubiquitinación
Límite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Cell Death Dis
Año:
2024
Tipo del documento:
Article
País de afiliación:
China