Induction of homologue of Slimb ubiquitin ligase receptor by mitogen signaling.

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.
Mesh Terms:
3T3 Cells, Animals, Blotting, Northern, Cell Differentiation, Cell Nucleus, Cell Transformation, Neoplastic, Dose-Response Relationship, Drug, Down-Regulation, Enzyme Activation, Fibroblasts, Genes, Dominant, Humans, Immunoblotting, Ligases, Mice, Mitogens, NF-kappa B, Ornithine Decarboxylase, Precipitin Tests, Signal Transduction, Time Factors, Tumor Cells, Cultured, Ubiquitin
J. Biol. Chem.
Date: Sep. 27, 2002
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