Jab1/CSN5 induces the cytoplasmic localization and degradation of RUNX3.
J Cell Biochem
; 107(3): 557-65, 2009 Jun 01.
Article
en En
| MEDLINE
| ID: mdl-19350572
ABSTRACT
Runt-related (RUNX) transcription factors play pivotal roles in neoplastic development and have tissue-specific developmental roles in hematopoiesis (RUNX1), osteogenesis (RUNX2), as well as neurogenesis and thymopoiesis (RUNX3). RUNX3 is a tumor suppressor in gastric carcinoma, and its expression is frequently inactivated by DNA methylation or its protein mislocalized in many cancer types, including gastric and breast cancer. Jun-activation domain-binding protein 1 (Jab1/CSN5), a component of the COP9 signalosome (CSN), is critical for nuclear export and the degradation of several tumor suppressor proteins, including p53, p27(Kip1), and Smad4. Here, we find that Jab1 facilitates nuclear export of RUNX3 that is controlled by CSN-associated kinases. RUNX3 sequestered in the cytoplasm is rapidly degraded through a proteasome-mediated pathway. Our results identify a novel mechanism of regulating nuclear export and protein stability of RUNX3 by the CSN complex.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Péptido Hidrolasas
/
Citoplasma
/
Péptidos y Proteínas de Señalización Intracelular
/
Subunidad alfa 3 del Factor de Unión al Sitio Principal
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
J Cell Biochem
Año:
2009
Tipo del documento:
Article
País de afiliación:
Corea del Sur