Tumor suppressor BAP1 nuclear import is governed by transportin-1.
J Cell Biol
; 221(6)2022 06 06.
Article
en En
| MEDLINE
| ID: mdl-35446349
ABSTRACT
Subcellular localization of the deubiquitinating enzyme BAP1 is deterministic for its tumor suppressor activity. While the monoubiquitination of BAP1 by an atypical E2/E3-conjugated enzyme UBE2O and BAP1 auto-deubiquitination are known to regulate its nuclear localization, the molecular mechanism by which BAP1 is imported into the nucleus has remained elusive. Here, we demonstrated that transportin-1 (TNPO1, also known as Karyopherin ß2 or Kapß2) targets an atypical C-terminal proline-tyrosine nuclear localization signal (PY-NLS) motif of BAP1 and serves as the primary nuclear transporter of BAP1 to achieve its nuclear import. TNPO1 binding dissociates dimeric BAP1 and sequesters the monoubiquitination sites flanking the PY-NLS of BAP1 to counteract the function of UBE2O that retains BAP1 in the cytosol. Our findings shed light on how TNPO1 regulates the nuclear import, self-association, and monoubiquitination of BAP1 pertinent to oncogenesis.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Señales de Localización Nuclear
/
Transporte Activo de Núcleo Celular
/
Beta Carioferinas
/
Proteínas Supresoras de Tumor
/
Ubiquitina Tiolesterasa
Límite:
Humans
Idioma:
En
Revista:
J Cell Biol
Año:
2022
Tipo del documento:
Article
País de afiliación:
Taiwán