RESUMO
Ubiquitin-like (UBL)-ubiquitin-associated (UBA) proteins, including Dsk2 and Rad23, act as delivery factors that target polyubiquitinated substrates to the proteasome. We report here that the Dsk2 UBL domain is ubiquitinated in yeast cells and that Dsk2 ubiquitination of the UBL domain is involved in Dsk2 stability, depending on the Dsk2 UBA domain. Also, Dsk2 lacking ubiquitin chains impaired ubiquitin-dependent protein degradation and decreased the interaction of Dsk2 with polyubiquitinated proteins in cells. Moreover, Dsk2 ubiquitination affected ability to restore the temperature-sensitive growth defect of dsk2Δ. These results indicate that ubiquitination in the UBL domain of Dsk2 has in vivo functions in the ubiquitin-proteasome pathway in yeast.
Assuntos
Proteínas de Ciclo Celular/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Ubiquitina/metabolismo , Ubiquitinação , Ubiquitinas/metabolismo , Sequência de Aminoácidos , Proteínas de Ciclo Celular/química , Proteínas de Ciclo Celular/genética , Dados de Sequência Molecular , Estabilidade Proteica , Estrutura Terciária de Proteína , Proteínas de Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/genética , Ubiquitinas/química , Ubiquitinas/genéticaRESUMO
Hepatocellular carcinoma (HCC) in a liver with advanced-stage chronic hepatitis C (CHC) is induced by hepatitis C virus, which chronically infects about 170 million people worldwide. To elucidate the associations between gene groups in hepatocellular carcinogenesis, we analyzed the profiles of the genes characteristically expressed in the CHC and HCC cell stages by a statistical method for inferring the network between gene systems based on the graphical Gaussian model. A systematic evaluation of the inferred network in terms of the biological knowledge revealed that the inferred network was strongly involved in the known gene-gene interactions with high significance (P < 10(-4)), and that the clusters characterized by different cancer-related responses were associated with those of the gene groups related to metabolic pathways and morphological events. Although some relationships in the network remain to be interpreted, the analyses revealed a snapshot of the orchestrated expression of cancer-related groups and some pathways related with metabolisms and morphological events in hepatocellular carcinogenesis, and thus provide possible clues on the disease mechanism and insights that address the gap between molecular and clinical assessments.