Induction of homologue of Slimb ubiquitin ligase receptor by mitogen signaling.
J Biol Chem
; 277(39): 36624-30, 2002 Sep 27.
Article
em En
| MEDLINE
| ID: mdl-12151397
ABSTRACT
Homologue of Slimb (HOS) is the substrate-recognizing component of the SCF(HOS)-Roc1 E3 ubiquitin protein ligase. This ligase mediates ubiquitination of the inhibitor of NF-kappaB transcription factor (IkappaB). We have found that HOS is highly expressed in a number of human cancer cell lines. The rates of the HOS gene transcription as well as HOS mRNA and protein levels were up-regulated in cells treated with mitogens or transfected with the inducers of mitogen-activated protein kinase pathway. Conversely, mitogen withdrawal strikingly reduced HOS levels during differentiation of mouse myoblasts. Activators of mitogen-activated protein kinase accelerated IkappaBalpha degradation and increased NF-kappaB transcriptional activity. Inhibition of HOS function via expression of dominant negative HOS (HOS(DeltaF)) initiated mouse myoblast differentiation and prevented Ras-mediated acceleration of IkappaBalpha degradation as well as NF-kappaB trans-activation and transformation of NIH3T3 cells. These data link the induction of HOS in proliferating cells with mitogen-signaling-dependent inhibition of cell differentiation and promotion of cell transformation.
Buscar no Google
Base de dados:
MEDLINE
Assunto principal:
Ubiquitina
/
Ligases
/
Mitógenos
Idioma:
En
Ano de publicação:
2002
Tipo de documento:
Article
País de afiliação:
Estados Unidos