A novel mechanism of nuclear factor kappaB activation through the binding between inhibitor of nuclear factor-kappaBalpha and the processed NH(2)-terminal region of Mig-6.
Cancer Res
; 62(20): 5668-71, 2002 Oct 15.
Article
em En
| MEDLINE
| ID: mdl-12384522
ABSTRACT
Mitogene-inducible gene-6 (Mig-6), an adaptor molecule containing the Cdc42/Rac interaction and binding (CRIB) domain, is rapidly induced by mitogenic and stressful stimuli, and sustained mig-6 expression is observed in chronic pathological conditions. The function of this molecule has remained elusive. We find that mig-6 is constitutively expressed in many human cancer cell lines, and Mig-6 is cleaved into the NH(2)-terminal region containing the CRIB domain and the remainder of the COOH-terminal region by limited proteolytic processing. We report here that full-length Mig-6, but not CRIB domain-deleted Mig-6 (DeltaMig-6) or uncleavable mutant of Mig-6 (Mig-6-S38A), induces transcriptional activation of nuclear factor of kappaB (NFkappaB), which is inhibited by inhibitor of kappaBalpha (IkappaBalpha), and that the processed NH(2)-terminal region of Mig-6 but not the full length is bound with IkappaBalpha through its NFkappaB binding region. These findings suggest that the processed CRIB domain of Mig-6 will compete with NFkappaB for IkappaBalpha and result in NFkappaB activation. This novel NFkappaB activation pathway provides new insights regarding tumorigenesis, and the specific inhibition of the cleavage of Mig-6 may be a target for clinical treatment.
Buscar no Google
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Transporte
/
NF-kappa B
/
Proteínas I-kappa B
/
Proteínas Adaptadoras de Transdução de Sinal
/
Proteínas de Ligação a DNA
Limite:
Humans
Idioma:
En
Ano de publicação:
2002
Tipo de documento:
Article